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Background Defective nasal barrier function is implicated in allergic rhinitis, which results in persistent inflammation and clinical symptoms, among which congestion plays a prominent role. In searching ways to improve the efficacy of nasally applied drugs in this condition, we tested the hypothesis that hydroxypropylmethylcellulose (HPMC), known as a mucoprotective agent, could enhance the efficacy of a decongestant (oxymetazoline nasal spray, 0.05%) by "sealing" it to the mucosa. Methods This double-blind placebo-controlled study was conducted with 40 patients (mean age, 35 years; 23 women) with persistent allergic rhinitis. The patients were randomized to receive 1 puff of oxymetazoline, followed by 1 puff of either HPMC or lactose powder (placebo) twice a day for 7 days and then only oxymetazoline rescue medication for another week. Peak inspiratory nasal flow (PNIF) was measured for 360 minutes after oxymetazoline and HPMC or placebo insufflation on days 1 and 8, and at a single point on day 15. Symptoms assessments involve visual analog scales and total nasal symptom scores. Results HPMC significantly enhanced oxymetazoline-increased PNIF at days 1 (p = 0.042) and 8 (p = 0.006). Baseline PNIF was greater in the HPMC group at day 15 (p = 0.014), indicative of further reduced nasal congestion. All nasal symptoms improved in both groups at day 8, but only the HPMC group showed further amelioration at day 15. Rescue medication was smaller in the HPMC group between days 8 and 15. Conclusion HPMC enhances decongestion through mucoadhesion but may also be augmenting the mucosal barrier in allergic rhinitis, which explains the carryover efficacy of oxymetazoline for a week after its discontinuation. Clinical trial registration clinicaltrials.gov identifier: NCT01986582.

Background: Omalizumab has been introduced for treatment of severe steroid dependent asthma in Bulgaria since 2009. We analyzed its effectiveness in a patient population eligible for reimbursement according the National Health Insurance Fund criteria. Methods: We reviewed the records of all asthmatics put on omlizumab treatment through an established selection process in one of the 2 centers in the country. The variables included demographic data, disease and smoking history, spirometry, total IgE, blood eosinophils, success of treatment as judged by patients and doctors, discontinuation of systemic steroids, adverse events. Results: A total of 76 patients (52 women, 68%) on omalizumab had data from at least two visits 6 months apart. All were atopic with total IgE ranging from 81 to 1466 (median 302) IU/mL. Baseline FEV1 % predicted was 47.7%±5.8% [mean±s.e.m.] and blood eosinophils 410±48 cells/mcL. 13 patients (17%) discontinued treatment: 9 patients not experiencing subjective improvement, 3 patients having no effect as judged by their doctors, and 1 patient because of anaphylaxis. Binary logistic regression associated success of treatment positively with age and negatively with preceding asthma duration and pack years of smoking: odds ratio for success in relation to age was 1.065, 95% CI [1.004-1.130], P=0.04; to asthma duration 0.951 [0.904-1.001], P=0.05; to pack years 0.927 [0.864 -0.995], P=0.04. Conclusions: The majority (83%) of consecutive severe asthmatics on omalizumab in real-life patient population met the goals of treatment, with age as positive predictor of success; asthma duration and smoking were associated with the odds of failure.

Cyclosporin A (Sandimmune®, Neoral®; Novartis) is a cyclic hydrophobic undecapeptide used to prevent and treat organ transplantation rejection. Cyclosporin A has potential therapeutic applications in the treatment of diseases such as asthma, psoriasis, atopic dermatitis and rheumatoid arthritis, but its wide use is limited by its poor bioavaliability and toxicity, the most significant of which is nephrotoxicity. There has been a tremendous research effort in producing cyclosporin analogues with better pharmacological profiles. This paper will give a general overview of the recent advances (1999 – 2002) made in producing novel semisynthetic cyclosporin analogues with improved bioavailability and therapeutic index.

Background In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it. Methods We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster®, Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), “top responders”, were then compared with those below the 25th percentile (n = 15) “poor responders”. Results On average, the 59 patients completing the study (mean age± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P

Cyclosporin A is effective in the treatment of asthma patients, but its chronic use is limited by toxicity. Novel cyclosporin A analogues were synthesized utilizing the olefin metathesis reaction and evaluated in a calcineurin A inhibition assay. The novel analogues demonstrated activity comparable to activity of the parent molecule and are potential soft drugs.

[reaction: see text] A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction. Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides. This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.