Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Assessment of dose-dependent reproductive toxicity of diclofenac sodium in male rats.

Diclofenac sodium is widely used in the non-steroidal anti-inflammatory drug in the treatment of pain and inflammation. It is also particularly associated with its adverse effects on avian fauna and linked to environmental issues. The present study was aimed to assess the dose-dependent toxicity of diclofenac sodium on a male reproductive system of rats. Four groups of healthy adult fertile male rats were administered with saline (control) or 0.25 mg/kg, 0.50 mg/kg and 1.0 mg/kg of diclofenac sodium, respectively for 30 days. Alterations in body and organ weight, sperm and testicular cell population dynamics, serum biochemistry, histopathology, and hematology were investigated as per aimed objectives. Diclofenac sodium treatment significantly (p ≤ 0.001) reduced weights of testis, epididymis, ventral prostate and seminal vesicle. Sperm count, sperm density (in epididymis and testis), sperm motility and testicular cell population dynamics were lowered in a dose-dependent manner. Administration of diclofenac exhibited varying degrees of degeneration testis, abnormal histo-architectures, and shrinkages in seminiferous tubules, particularly in higher doses. Diclofenac sodium treatments also altered hepatic and renal function parameters significantly. In conclusion, it may claim that diclofenac sodium treatment altered reproductive metabolic status, androgenic activities and histo-architecture of the testis of male rats and induced hepatotoxicity and renal toxicity.

Synthetic and phytocompounds based dipeptidyl peptidase-IV (DPP-IV) inhibitors for therapeutics of diabetes.

Currently antidiabetic therapeutic strategies are mainly based on synthetic hypoglycemic agent. Antidiabetic drugs are associated with significant adverse effects of hypoglycemia, dysfunction of insulin and weight gain. Nowadays, the novel Dipeptidyl peptidase-IV (DPP-IV) inhibitors unique approach for the management of diabetes has been considered to be safe, as DPP-IV inhibitors reduce blood glucose level by monitoring hyperglycemia including positive effects on body weight as it remains neutral, improves glycated hemoglobin levels and do not induce hypoglycemia. Inhibitors help to protect degradation of Glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), gut hormones which helps to suppresses postprandial glucagon release, delay gastric emptying and regulate satiety. Therefore, the innovation of DPP-IV inhibitor based drugs regulates activity of incretin hormones such as GLP-1 and GIP. Commercially available DPP-IV inhibitors are chemically synthesized with good therapeutic value. However, the durability and long-term safety of DPP-IV inhibitors remains to be established. On the other hand, phytocompounds-based DPP-IV inhibitors are alternative and safe to use as compared to synthetic. Numerous novel antidiabetic compounds and group of compounds emerging in clinical development are through DPP-IV inhibition. This review summarized recent progress made on DPP-IV inhibitors from both synthetic as well as from natural sources.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut allergy across Europe. METHODS: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets.

The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy.

Health-related quality of life in food-allergic adults from eight European countries.

BACKGROUND: Food allergy can impair health-related quality of life (HRQL). Food Allergy Quality of Life Questionnaires (FAQLQs) have been developed and validated, including an adult form (FAQLQ-AF). HRQL has not, to date, been measured across different European countries using a uniform methodology. OBJECTIVE: To translate and validate the FAQLQ-AF for use in 8 European countries (Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden). METHODS: The English FAQLQ-AF was translated, back-translated, and compared for use in the 8 relevant European languages. Adults with a perceived food allergy were recruited from outpatient departments and through a community survey. Participants completed the FAQLQ-AF, the Food Allergy Independent Measure, and questions concerning participants' characteristics. Validity of the FAQLQ-AF was analyzed for use in the 8 countries. RESULTS: The FAQLQ-AF had strong construct validity (r > 0.59) and an excellent internal consistency (Cronbach α > 0.95) in all countries. Total FAQLQ-AF scores (range 3.2-5.0) were significantly different across participating countries. CONCLUSION: The FAQLQ-AF is a suitable and valid instrument for measuring HRQL in food-allergic adults in Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden. The impact of food allergy on HRQL seems to differ among adults from the 8 participating European countries.

Kiwifruit allergy across Europe: clinical manifestation and IgE recognition patterns to kiwifruit allergens.

BACKGROUND: Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions. OBJECTIVE: We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated. METHODS: This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP. RESULTS: Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract. CONCLUSION: Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.

Health sector costs of self-reported food allergy in Europe: a patient-based cost of illness study.

INTRODUCTION: Food allergy is a recognized health problem, but little has been reported on its cost for health services. The EuroPrevall project was a European study investigating the patterns, prevalence and socio-economic cost of food allergy. AIMS: To investigate the health service cost for food-allergic Europeans and the relationship between severity and cost of illness. METHODS: Participants recruited through EuroPrevall studies in a case-control study in four countries, and cases only in five countries, completed a validated economics questionnaire. Individuals with possible food allergy were identified by clinical history, and those with food-specific immunoglobulin E were defined as having probable allergy. Data on resource use were used to estimate total health care costs of illness. Mean costs were compared in the case-control cohorts. Regression analysis was conducted on cases from all 9 countries to assess impact of country, severity and age group. RESULTS: Food-allergic individuals had higher health care costs than controls. The mean annual cost of health care was international dollars (I$)2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95% confidence interval I$324-I$1530). A similar result was found for adults in each country, and for children, and was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. CONCLUSIONS: Food allergy is associated with higher health care costs. Severity of allergic symptoms is a key explanatory factor.

Varying allergen composition and content affects the in vivo allergenic activity of commercial Dermatophagoides pteronyssinus extracts.

BACKGROUND: Diagnosis and immunotherapy of house-dust mite (HDM) allergy is still based on natural allergen extracts. The aim of this study was to analyze commercially available Dermatophagoides pteronyssinus extracts from different manufacturers regarding allergen composition and content and whether variations may affect their allergenic activity. METHODS: Antibodies specific for several D. pteronyssinus allergens (Der p 1, 2, 5, 7, 10 and 21) were used to analyze extracts from 10 different manufacturers by immunoblotting. Sandwich ELISAs were used to quantify Der p 1 and Der p 2 in the extracts. Mite-allergic patients (n = 45) were skin-tested with the extracts and tested for immunoglobulin E (IgE) reactivity to a panel of 10 mite allergens (Der p 1, 2, 4, 5, 7, 8, 10, 14, 20 and 21) by dot blot. RESULTS: Only Der p 1 and Der p 2 were detected in all extracts but their concentrations and ratios showed high variability (Der p 1: 6.0-40.8 µg ml(-1); Der p 2: 1.7-45.0 µg ml(-1)). At least 1 out of 4 allergens (i.e. Der p 5, 7, 10 and 21) was not detected in 8 of the studied extracts. Mite-allergic subjects showed different IgE reactivity profiles to the individual mite allergens, the extracts showed different allergenic activity in skin-prick tests and false-negative results. CONCLUSIONS: Commercially available D. pteronyssinus extracts lack important allergens, show great variability regarding allergen composition and content and some gave false-negative diagnostic test results in certain patients.

Correction: Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits.

[This corrects the article DOI: 10.1371/journal.pone.0264646.].

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits.

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.

Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans.

CONTEXT: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. OBJECTIVE: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of W. coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities. MATERIAL AND METHODS: The identification of phytoconstituents of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic rats. RESULTS: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay as well as significantly inhibit serum DPP-4 levels. Accordingly, the administration of the ethanol fruit extract resulted in a significant (P ≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein-ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. CONCLUSION: It can be concluded that the phytoconstituents of an ethanol fruit extract of W. coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

Estimating the Risk of Severe Peanut Allergy Using Clinical Background and IgE Sensitization Profiles.

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54-0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis.

BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years. RESULTS: Significant reductions (about 50%) in rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025; birch extract, P = .0063), and skin sensitivities (P < .0001) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons. Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels, which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups. New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract, but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients. No severe systemic adverse events were observed in the rBet v 1-treated group. CONCLUSION: The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.

Inhibition of allergen-induced wheal and flare reactions by levocetirizine and desloratadine.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The reproducible and standardized histamine-induced wheal and flare model helps identify the objective effectiveness of antihistamines in humans, as well as their differences in onset and duration of action. Some of the newest antihistamines have already been compared in a head-to-head setting using this model. However, their objective action at inhibiting the allergen-induced wheal and flare response has not been reported yet. WHAT THIS STUDY ADDS: The time-response study presented here shows the objective activity of two of the newest generation of antihistamines, levocetirizine and desloratadine, at inhibiting the allergen-induced wheal and flare response in a randomized, cross over, placebo-controlled trial. This model is interesting to the clinical setting since allergic subjects are recruited, and the response to allergen involves mast cell degranulation and release of numerous vasoactive and pro-inflammatory mediators additionally to histamine. In addition, this study reports receptor occupancy for both antihistamines at therapeutic dosage, leading to analysis of potential differences in activity. This study clearly shows the potential anti-inflammatory properties of desloratadine and levocetirizine in their skin activity when allergen is the challenging agent as occurs in the clinical situation. AIMS: To evaluate the inhibitory activity of the new-generation antihistamines levocetirizine and desloratadine at their therapeutic doses on the allergen-induced wheal and flare reaction at 1.5 h, 4 h, 7 h, 12 h and 24 h postdose, and to measure their plasma and skin concentrations. METHODS: A double-blind, randomized, cross-over, placebo-controlled study in 18 allergic subjects was carried out. The time-response of the wheal and flare reaction areas under the curve (AUC) were compared by anova. RESULTS: Both antihistamines significantly (P < 0.001) inhibited the allergen-induced wheal and flare reactions compared with placebo. Levocetirizine was significantly more potent than desloratadine. Mean +/- SEM wheal AUC(0-24 h) was 506.4 +/- 81.0 with levocetirizine and 995.5 +/- 81.0 mm(2) h with desloratadine as compared with placebo (1318.5 +/- 361.0 mm(2) h). Flare AUC(0-24 h) was 5927.3 +/- 1686.5 and 15838.2 +/- 1686.5 mm(2) h, respectively [P < 0.001 for both compared with placebo (22508.2 +/- 7437.1 mm(2) h)]. Levocetirizine showed significant inhibition of wheal and flare already at 1.5 h postdose compared with placebo (P

Bronchial challenge test in asthmatics sensitized to mites: role of particle size in bronchial response.

Although major house dust mite allergen (Der p 1) is carried mainly on large particles (>10 microm), standard bronchial challenge tests (BCT) use nebulizers that deliver smaller particles (sizes from 1 to 5 microm) and may therefore not reflect actual domestic exposure. The objective of this study was to evaluate the influence of particle size of Dermatophagoides pteronyssinus extract on bronchial response. Specific BCT were performed with different mass median aerodynamic diameters (MMAD): 1.1, 5.6, and 9.7 microm. Each of the 19 mite-sensitized patients underwent mite BCT three times, once with each nebulizer. IL-5 levels were assessed in induced sputum and blood samples. The PD(20) for Der p 1 differed substantially with particle size, with less Der p 1 (11.2 ng) needed to produce a PD(20) with the largest particles (9.7 microm), compared to 18.1 ng for the 5.6 microm particles and 142.5 ng for the 1.1 microm particles (p < 0.0001). Large particles also induced an early phase response significantly more often than small particles (100% vs. 63%). Although the late phase reaction (LPR) frequency was similar with all three particle sizes, lower mean oral corticosteroid doses were needed to treat LPR with the largest particles (23 mg), compared to the smaller particles, with 34 mg for the 5.6 microm particles and 51 mg for the 1.1 microm. The 1.1 microm particles produced a significantly greater increase in IL-5 concentrations in sputum and blood compared to the larger particles. Large particles clearly play a role in the immediate bronchial response in asthmatics sensitized to mites and, therefore, should be included in pharmacological studies in humans.

Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats.

Aspirin (acetylsalicylic acid) is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte) count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60-day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry.

Hypolipidaemic efficacy of Capparis decidua fruit and shoot extracts in cholesterol fed rabbits.

High fat diet caused significant (8-fold) increase in serum total cholesterol in rabbits. Administration of C. decidua fruit extract (50% ethanolic) at the dose of 500 mg/kg body weight significantly reduced serum total cholesterol (61%), LDL cholesterol (71%), triglycerides (32%) and phospholipids (25%). Similarly C. decidua shoot extract lowered serum total cholesterol (48%), LDL cholesterol (57%), triglycerides (38%) and phospholipids (36%). The cholesterol content of aorta was decreased by 44 and 28% in fruit and shoot extract treatment respectively. The HDL to total cholesterol ratio and atherogenic index was significantly decreased in plant extract treated groups suggesting antiatherosclerotic nature of these plant extract. These results reveal the hypolipidaemic potential of C. decidua fruit and shoot.