IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study.

BACKGROUND: We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut-allergic population characterized under a common protocol. METHODS: Sixty-eight peanut-allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting dose was established by double-blind placebo-controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. RESULTS: Seventy-eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut-allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early-onset peanut allergy. Peanut-tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA /l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA /l is significantly associated with the development of systemic reactions to peanut.

Characterization of profilin and polcalcin panallergens from ash pollen

Background: Ash ( Fraxinus excelsior ) is an important source of allergenic pollen in temperate areas of Europe. Profilin and polcalcin are 2 important panallergens involved in cross-reactivity between different sources. Objective: To clone and produce Fra e 2 (profilin) and Fra e 3 (polcalcin) as recombinant proteins and evaluate their immunological properties using the natural forms obtained from ash pollen. Methods: Total RNA from ash pollen was used as a template to obtain the specific complementary DNA (cDNA) sequences of the 2 panallergens. The cDNA-encoding sequences were cloned into the pET11b expression vector and used to transform BL21 (DE3) Escherichia coli cells. Proteins were expressed, purified by chromatography, and characterized structurally by circular dichroism, mass spectrometry, and immunologically by western blot and ELISA using profilin and polcalcin polyclonal antibodies and human sera from ash pollen-sensitized patients. Results: Profilin and polcalcin amino acid sequences from ash pollen showed a high degree of identity with homologous allergens from different sources. The cDNA-encoding allergen sequences were expressed as nonfusion recombinant proteins and purified to homogeneity. Secondary structure values were similar to those obtained from other members of these families. Allergenic properties of the recombinant allergens were observed to be equivalent to those of the natural counterparts of F excelsior pollen. Conclusions: Fra e 2 and Fra e 3 recombinant allergens might be used in clinical diagnosis to determine profilin- and polcalcin-specific IgE levels present in the sera of ash pollen-sensitized patients, thus facilitating the finding of the sensitizing source in areas with complex sensitization profiles (AU)

Antecedentes: El polen de fresno (Fraxinus excelsior ) es una importante fuente alergénica en zonas cálidas de Europa. La profilina y polcalcina son 2 panalérgenos implicados en reactividad cruzada. Objetivos: Clonar y producir Fra e 2 (profilina) y Fra e 3 (polcalcina) como alérgenos recombinantes. Comparar sus propiedades inmunológicas con sus formas naturales del polen de fresno. Métodos: El RNA total de polen de fresno se utilizó como molde para obtener los cDNAs específicos de ambos panalérgenos. Dichos cDNAs se clonaron en el vector de expresión pET11b y se transformaron células de Escherichia coli BL21(DE3). Las proteínas se caracterizaron mediante dicroísmo circular, espectrometría de masas, inmunodetección en membrana y ELISA utilizando anticuerpos policlonales frente a profilina y polcalcina y sueros de pacientes alérgicos al polen de fresno. Resultados: Las secuencias de aminoácidos de la profilina y polcalcina de polen de fresno presentaban una identidad de secuencia elevada con alérgenos homólogos. Dichos alérgenos se expresaron como proteínas recombinantes independientes y se purificaron a homogeneidad. Los valores de estructura secundaria fueron similares a los de otros miembros de estas familias. Las propiedades alergénicas de los alérgenos recombinantes resultaron ser equivalentes a los de sus homólogos naturales del polen. Conclusiones: Los alérgenos recombinantes Fra e 2 y Fra e 3 podrían usarse en diagnóstico clínico para determinar los niveles de IgE específicos para profilina y polcalcina en los sueros de los pacientes sensibilizados al polen de fresno, facilitando así la identificación de la fuente sensibilizante en áreas donde los pacientes presentan perfiles alergénicos complejos (AU)

Effects of aromatase inhibitors and body mass index on steroid hormone levels in women with early and advanced breast cancer.

BACKGROUND: Aromatase inhibitors (AIs) are central to the management of oestrogen receptor-positive breast cancer in the adjuvant and metastatic setting. Levels of circulating steroid hormones (SHs) were measured in patients established on AIs to investigate: the influence of body mass index (BMI) in both the adjuvant and metastatic setting; the class of AI utilized in the adjuvant setting (steroidal versus non-steroidal); and differences in SH levels between women treated adjuvantly and those receiving a second-line AI for locally advanced/metastatic disease. METHODS: Plasma levels of androstenedione, 5-androstene-3ß,17ß-diol, dehydroepiandrosterone, oestradiol and testosterone were measured by radioimmunoassay in women with breast cancer who were receiving AIs in either an adjuvant or a metastatic setting. Differences between mean SH levels by class of AI, BMI, and second-line versus adjuvant therapy were assessed. RESULTS: Sixty-four women were receiving AI therapy, 45 (70 per cent) in an adjuvant setting and 19 (30 per cent) were taking a second-line AI. There was no significant correlation between BMI and SH levels. However, BMI was significantly higher in the second-line AI cohort compared with the adjuvant cohort (29.8 versus 26.2 kg/m2 respectively; P = 0.026). In the adjuvant setting, patients receiving a steroidal AI had significantly higher levels of all five hormones (P < 0.050). In the second-line AI cohort, oestradiol levels were significantly higher than in the adjuvant cohort (4.5 versus 3.3 pg/ml respectively; P = 0.022). Multivariable analysis adjusted for BMI confirmed the higher residual oestradiol level in the second-line AI group (P = 0.063) and a significantly higher androstenedione level (P = 0.022). CONCLUSION: Residual levels of SH were not significantly influenced by BMI. However, the significant differences in residual SH levels between the second-line and adjuvant AI cohort is of relevance in the context of resistance to AI therapy, and warrants further investigation.

Nonallergic airway hyperresponsiveness and allergen-specific IgE levels are the main determinants of the early and late asthmatic response to allergen.

BACKGROUND: Conflicting results have been reported in studies of predictive factors for airway responsiveness to allergens during bronchial challenges. OBJECTIVE: The aim of this study was to assess determinants of airway responsiveness to 3 different allergens during standardized bronchial challenges. METHODS: Data were collected from asthmatic patients who participated in allergen challenge trials between 2000 and 2006 (cat, n = 37; house dust mite [HDM], n = 35; grass pollen, n = 27). PD20 (provocative dose causing a 20% fall in forced expiratory volume in the first second) methacholine, PD20 allergen, allergen skin test endpoint, allergen-specific immunoglobulin (Ig) E levels, and late asthmatic response were analyzed for each allergen group. RESULTS: During the early asthmatic response, a significant relationship was found between PD20 allergen and PD20 methacholine (P < .01 for cat, HDM, and grass pollen), as well as between PD20 allergen and allergen-specific IgE levels (P < .05 for cat and HDM). No relationship was observed between PD20 allergen and allergen skin test endpoint (P > .05). Late asthmatic response was significantly more frequent after HDM challenge than after cat or grass pollen challenges (57.1% vs16.2% and 33.3%, P < .01). Dual responders during HDM challenges had significantly higher allergen-specific IgE levels (P < .05) and higher nonallergic airway responsiveness (P < .05). CONCLUSION: Nonallergic airway hyperresponsiveness and allergen-specific IgE levels were the main determinants of early and late asthmatic responses. HDM challenges were the most interesting model with regard to the occurrence of late asthmatic response. In contrast to previous publications and to the official statement on standardized challenge testing with sensitizing stimuli, skin sensitivity appears to be a poor predictor of the early asthmatic response.

Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives.

BACKGROUND: Birch pollen and pollen from related trees of the Fagales order are a major cause of allergic rhinitis, conjunctivitis, and asthma through the spring season in northern and central Europe. OBJECTIVE: To investigate the clinical effects of injection immunotherapy with genetically modified derivatives of major birch pollen allergen Bet v 1 on pollen-induced allergic symptoms. METHODS: A three-arm double-blind placebo-controlled immunotherapy study was conducted with one pre-seasonal course of treatment using two derivatives of Bet v 1, namely a recombinant Bet v 1 trimer and an equimolar mixture of two recombinant Bet v 1 fragments together representing the whole protein sequence. Analysis of local and systemic adverse events was performed for 124 patients who had received at least one dose of medication. Clinical efficacy was monitored by symptom medication scores and interval scoring in the per protocol-treated population (n=84). In addition, skin and nasal provocation responses and allergen-specific antibodies were assessed. RESULTS: There were trends towards improvement in the subjects' well-being and clinical symptoms (nasal scores), although comparisons with a placebo group did not show statistical significance in the main end-point, the combined symptom medication score. Reductions in skin and nasal sensitivity were observed for some subjects with a trend for the Bet v 1 trimer to be more effective than the fragments. Treatment induced strong IgG1 and IgG4 allergen-specific antibody responses. Local injection-site reactions were most frequent in the trimer group affecting 59.5% of patients as opposed to 37.8% and 30.6% in the fragment and placebo groups, respectively. Systemic reactions were elicited more frequently by fragments. A large proportion of adverse side-effects appeared hours following injections, and might be attributable to concurrent exposure to related pollens. CONCLUSION: Single courses of injection immunotherapy with Bet v 1 allergen derivatives showed trends towards improved well-being and reduced reactivity to specific allergen provocation, but did not yield significant improvement in the combined symptom medication score in this study.

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to Fc epsilon RI.

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.

Vaccination with genetically engineered allergens prevents progression of allergic disease.

IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.

The allergen profile of ash (Fraxinus excelsior) pollen: cross-reactivity with allergens from various plant species.

BACKGROUND: Ash, a wind-pollinated tree belonging to the family Oleaceae, is distributed world-wide and has been suggested as a potent allergen source in spring time. OBJECTIVE: The aim of this study was to determine the profile of allergen components in ash pollen in order to refine diagnosis and therapy for patients with sensitivity to ash pollen METHODS: The IgE reactivity profile of 40 ash pollen-allergic patients was determined by immunoblotting. Antibodies raised to purified pollen allergens from tree and grass pollens were used to identify cross-reactive structures in ash pollen extract. IgE immunoblot inhibition studies were performed with recombinant and natural pollen allergens to characterize ash pollen allergens and to determine the degree of cross-reactivity between pollen allergens from ash, olive, birch, grasses and weeds. RESULTS: The allergen profile of ash pollen comprises Fra e 1, a major allergen related to the major olive allergen, Ole e 1, and to group 11 grass pollen allergens, the panallergen profilin, a two EF-hand calcium-binding protein, a pectinesterase-like molecule and an allergen sharing epitopes with group 4 grass pollen allergens. Thus, the relevant allergens of ash are primarily allergens that share epitopes with pollen allergens from other tree, grass and weed species. CONCLUSIONS: Allergic symptoms to ash pollen can be the consequence of sensitization to cross-reactive allergens from other sources. The fact that ash pollen-allergic patients can be discriminated on the basis of their specific IgE reactivity profile to highly or moderately cross-reactive allergens has implications for the selection of appropriate forms of treatment.

Anaphylactic reactions after therapeutic injection of mistletoe (Viscum album L.).

Mistletoe (Viscum album) is a plant that is semiparasitic of several trees: apple, oak, pine trees, etc. Because of the probable cytolytic action of one of the leaf's most abundant composites, in some countries mistletoe is used as a complementary medicine. Although only a few adverse reactions have been noted (cephalea, fever), cases of anaphylactic shock have been described. We present three cases of severe reaction after injection of mistletoe extract. Two of the patients had cancer. The third, whose brother had cancer, used the plant for preventive purposes. We discuss the danger of possible severe reactions due to the use of products employed in so-called alternative therapies.

Anaphylactic reactions after therapeutic injection of mistletoe (Viscum album L.)

Mistletoe (Viscum album) is a plant that is semiparasitic of several trees: apple, oak, pine trees, etc. Because of the probable cytolytic action of one of the leaf's most abundant composites, in some countries mistletoe is used as a complementary medicine. Although only a few adverse reactions have been noted (cephalea, fever), cases of anaphylactic shock have been described. We present three cases of severe reaction after injection of mistletoe extract. Two of the patients had cancer. The third, whose brother had cancer, used the plant for preventive purposes. We discuss the danger of possible severe reactions due to the use of products employed in so-called alternative therapies (AU)

El Mistletoe (Viscum album) (muérdago o visco blanco) es una planta semiparásita de algunos árboles: manzano, roble, pino, etc., que por la probable acción citolítica de algún compuesto más abundante en las hojas, se emplea en algunos países en el tratamiento del cáncer como medicación complementaria. Aunque se han observado pocas reacciones adversas (cefalea, fiebre) se han descrito casos de choque anafiláctico. En este trabajo se presentan tres casos de reacción grave, tras la inyección de un extracto de la planta. Dos pacientes padecían cáncer y otro empleó el producto por prevención por el N hecho de que un hermano padecía cáncer. Se advierte de las posibles reacciones graves por el uso de productos utilizados en las llamadas terapias alternativas (AU)

Characteristics of cystic breast disease with special regard to breast cancer development.

BACKGROUND: This prospective study compares the characteristics of cystic disease of the breast (CDB) of patients who developed breast cancer (BCa) during the follow-up (1.25-4 years) period with those who did not. MATERIALS AND METHODS: K+, Na+, albumin, dehydroepiandrosterone (DHA), DHA-sulphate, oestrone, oestradiol, testosterone and progesterone levels were determined in breast cyst fluid (BCF). Patients presented data about their menstrual status, reproductive history, lactation period, date of first and the number of BCF aspirations, gynaecological interventions, use of oral contraceptives, family history of cancer, smoking habits and coffee consumption. The BCa incidence of patients was compared with the expected number of BCas in an age-matched group of 5143 women. RESULTS: Out of 147 patients 6 developed BCa. The standardized incidence rate was 6.29. There were significant differences in testosterone, oestrone and progesterone levels and also reproductive history of patients who developed BCa compared with patients without BCa. CONCLUSION: The above markers outline a subgroup of patients with the highest BCa risk.

Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population.

BACKGROUND: Bet v 1, the major allergen in birch pollen, is recognized by more than 90% of patients allergic to birch in northern and central Europe. Immunotherapy is commonly performed with birch pollen extracts. Recently, hypoallergenic derivatives of Bet v 1 (rBet v 1 fragments, rBet v 1 dimer and trimer) were constructed and purified. OBJECTIVE: Our aim was to compare the allergenic activity of wild-type rBet v 1 with recombinant Bet v 1 derivatives (rBet v 1 fragments, dimer and trimer) with potentially reduced anaphylactic activity by skin testing in a French population. METHODS: Among the 36 birch pollen allergic patients included in the study, 29 were tested by skin prick testing and 30 by intradermal injections with purified monosubstances: rBet v 1 fragments (F1: aa1-74 and F2: aa75-160), Bet v 1 dimer and trimer. Intradermal tests were performed by the end-point intradermal titration method. Eight of the intradermally-tested patients were previously hyposensitized. Tests were performed over a period of 6 months (before, during and after birch pollen season); Bet v 1-specific IgE and IgG4 subclass responses were measured by immunoblotting and ELISA. RESULTS: All patients showed lower reactivity with the modified rBet v 1 allergens, both in skin prick and intradermal tests. In 25 and 23 out of 29 patients the lowest concentration of fragment 1 and 2, respectively, resulting in a positive prick test was 100-fold higher than the lowest concentration of monomer resulting in a positive prick test. For dimer it was 100-fold or more in 25 out of 29 patients, and for trimer it was 100-fold or superior in 26 out of 29 patients. By intradermal testing, the end-point concentration was 160-fold higher for trimer than for monomer in 24 patients and 40-fold higher in five patients. For the two fragments the end-point concentration was 160-fold higher in 20 out of 22 patients. CONCLUSION: Genetically modified hypoallergenic derivatives of the major birch pollen allergen, Bet v 1 showed reduced capacity to induce immediate type skin reactions. They may represent candidate molecules for immunotherapy of birch pollen allergy with reduced risk of anaphylactic side-effects.

Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy.

BACKGROUND: Type I allergic symptoms in the oropharyngeal mucosa upon contact with plant-derived food in patients with pollen allergies have been termed oral allergy syndrome (OAS). IgE cross-reactivity between pollen and food allergens represents the molecular basis for this phenomenon. The sensitizing allergen source (pollen or plant food) in OAS is a controversial issue. OBJECTIVE: We sought to determine the primary sensitizing molecules in patients with OAS. METHODS: We used recombinant birch pollen (rBet v 1 and rBet v 2) and plant food allergens (apple, rMal d 1; celery, rApi g 1; and carrot, rDau c 1), as well as natural pollen (birch and timothy grass) and plant food (apple, peach, kiwi, hazelnut, celery, and carrot) allergens, to identify cross-reactive allergens by using qualitative immunoblot inhibitions. In addition, we determined the percentage of plant food-specific IgE that can be preadsorbed with recombinant and natural pollen allergens by quantitative RAST inhibitions by using sera from 71 patients with OAS. RESULTS: Preincubation of sera with recombinant and natural pollen allergens led to an almost complete inhibition of IgE binding to plant food allergens in Western blots, as well as in RAST inhibition experiments. In contrast, recombinant plant food allergens poorly inhibited IgE binding to Bet v 1. CONCLUSION: Most IgE epitopes in plant food recognized by patients with OAS are resembled by pollen allergens. Thus pollen allergens may be responsible for the elicitation and maintenance of OAS.

Regulation of steroid sulphatase expression and activity in breast cancer.

Steroid sulphatase (STS) catalyzes the conversion of oestrone sulphate (E1S) to oestrone (E1) and its action in breast tumours makes a major contribution to in situ oestrogen production in this tissue. Although expression of STS mRNA and STS activity are increased in malignant breast tissues compared with that in non-malignant tissues, little is known about the regulation of its expression or activity. In the present study we have used a RT-PCR technique to investigate the regulation of STS mRNA expression in cultured breast tissue fibroblasts and MCF-7 cells. STS mRNA expression was readily detectable in fibroblasts derived from breast tissue proximal to tumours, breast tumour tissue and reduction mammoplasty tissue. For two pre-menopausal subjects, STS mRNA expression was similar in proximal and tumour fibroblasts whereas for a third, post-menopausal subject, expression in breast tumour fibroblasts was 2.4-fold that in proximal fibroblasts. The cytokine tumour necrosis factor alpha (TNFalpha) or the STS inhibitor, 2-methoxyoestrone-3-O-sulphamate, had no effect on STS mRNA expression in fibroblasts. STS mRNA was detectable in MCF-7 cells but neither TNFalpha nor interleukin 6 (IL-6) affected its expression. Transient transfection of COS-1 and MCF-7 cells with a STS cDNA lacking STS 5' and 3' sequences increased activity 17-fold and 2-fold, respectively. TNFalpha plus IL-6 increased STS activity in mock transfected MCF-7 cells and further increased STS activity in transfected MCF-7 cells. This indicates that activation can occur independently of STS promoter and enhancer elements. In conjunction with the lack of regulation of STS mRNA it suggest that TNFalpha and IL-6 may increase STS activity via a post-translational modification of the enzyme or by increasing substrate availability.

Inhibition of steroid sulphatase activity by tricyclic coumarin sulphamates.

The identification of the active pharmacophore required for potent inhibition of steroid sulphatase activity, i.e. an aryl-O-sulphamate structure, has led to the synthesis and testing of a large number of 1-4 ring-based inhibitors. 4-Methylcoumarin-7-O-sulphamate (COUMATE) was one of the first non-steroid based inhibitors identified. In an attempt to increase the potency of this class of inhibitor a series of tricyclic COUMATEs (665-6615 COUMATEs) have been synthesised and evaluated. Using placental microsomes as a source of oestrone sulphatase (E1-STS) the size of the third ring of the tricyclic COUMATEs was found to have a marked effect on inhibitor potency. Whereas 665- and 6615-COUMATEs had IC(50)s of 200 and 370 nM, respectively, the most potent inhibitor in vitro in this series was 6610 COUMATE with an IC(50) of 1 nM. Selected inhibitors were tested for their in vivo potency by administration of a single dose (0.1 or 1 mg/kg, p.o.) to female rats. Surprisingly, in vivo 6615 COUMATE proved to be the most active drug, inhibiting rat liver E1-STS activity by 23 and 94% when assayed 24 h after administration of the 0.1 and 1 mg/kg doses. E1-STS activity in brain tissue and white blood cells was also found to be inhibited when selected drugs were tested. These studies have identified a number of tricyclic COUMATEs with therapeutic potential.

Serum eosinophil cationic protein measurements in the management of perennial and periodic asthma: a prospective study.

We performed a prospective study in order: 1) to determine whether a correlation could be found between serum eosinophil cationic protein (ECP) levels and clinical and functional status in perennial asthmatics during a 5 month prospective study; and 2) to evaluate the relationship between allergic exposure and ECP levels in periodic asthmatics. Two groups of asthmatic patients were selected: a group of acutely ill perennial asthmatics and a group of periodic asthmatics. The acutely ill perennial asthmatics (n=22, mean age=39.4 yrs) were included on the basis of hospitalization for acute asthma. At the end of the hospitalization, there was a 5 month follow-up of clinical, functional and medication scores, as well as eosinophil counts and ECP levels. The periodic asthmatic group was composed of asthmatics sensitized to birch and tree pollens (n=10, mean age=33.8 yrs). The same measurement were performed on this group, before, during and after the pollen season. Under corticosteroid treatment in the acutely ill patients, there was a significant decrease in serum ECP levels between the first day of hospitalization and the day of discharge (mean: 23.2 microg x L(-1) and 9.5 microg x L(-1), respectively; p=0.006). No correlation was found between the clinical status, functional status and serum ECP levels during the 5 month follow-up. A significant increase in ECP levels was found in periodic asthmatics during the pollen season. Our results suggest that serum eosinophil cationic protein is a useful marker of allergen exposure and of acute asthma treatment. This could be of importance in the prevention and follow-up of allergic asthma; the value of serum eosinophil cationic protein measurements in the day-to-day management of adult asthmatics needs to be further clarified.

Preliminary evaluation of Leucaena leucocephala seed gum as a tablet binder.

The seed galactomannan of Leucaena leucocephala Lam. de Wit var.K-8 (family Leguminosae), a natural polysaccharide, with properties comparable to guar gum, was evaluated as a pharmaceutical binder. Characterization was done using studies of compressibility, micromeritic, and mechanical properties of granules prepared by wet granulation and subsequent studies on compacts, both containing 5% w/w of binder. The seed gum was subsequently used as a binder with a badly compressible material, paracetamol, and studied likewise. The seed gum compared will with standard pharmaceutical binders (starch and polyvinyl pyrrolidone [PVP] K30), at least for properties studied herein.

Modification in sucrose tolerance test with acarbose, guargum and their combination in patients with non-insulin dependent diabetes.

The study was undertaken to assess the efficacy guargum, Acarbose and their combination in modifying the sucrose absorption in patients of non Insulin dependent diabetes mellitus (NIDDM). Fifty patients of NIDDM were randomly distributed in three groups. Group A had 20 patients who received 20 grams of guargum, Group B had 10 patients who received 100 mg of Acrabose, Group C had 20 patients who received 10 grams of guargum and 50 grams of Acrabose. All the patients underwent 50 grams sucrose tolerance test with and without the trial drugs. Blood glucose levels were determined at 0, 30, 60, 90 and 120 minutes after sucrose loading. With the drugs, there was a significant decrease in the blood glucose levels at all time intervals (p < 001) in all the three groups. In all the three groups the blood glucose levels with the trial drugs was significantly lower (p < 001) than without the drug. It was seen that acarbose alone and guargum alone did not differ significantly in reducing the blood sugar level whereas combination of two produced significantly greater reduction in blood glucose levels than either of the drug used alone. Thus both guargum and acarbose are equally effective in modifying the absorption of sucrose. When combined in half the dosage they have synergistic effect and the reduction in blood glucose level is greater than either of the drug used alone.