piperidines and isospaglumic-acid

Allergic conjunctivitis is the most common form of conjunctivitis encountered in daily ophthalmological practice. Its therapy can be problematic: it must be simple, free of complications, and adaptable to everyday life.. We conducted a randomized prospective single-center survey on 102 patients between 4 and 80 years of age who presented moderate allergic conjunctivitis. Patients were divided into two groups, one treated in monotherapy with N-acetyl-aspartyl glutamic acid (NAAGA) over 4 weeks and the other treated with bi-therapy (NAAGA and Levocabastine during the first week and NAAGA only for the next 3 weeks), with evaluation of the sum of the scores of the cardinal signs of allergic conjunctivitis at D0, D7 and D28.. The two populations were homogeneous at inclusion: the majority of the patients had a history of allergies, with a nonspecific disrupted allergy workup (IgE and eosinophils) and a higher initial score for the children included in the study. The scores decreased sharply at D7 (50% reduction) and at D28 (bordering 1) with no significant difference between the two groups. Tolerance to the treatment judged by unusual sensations upon instillation was better for the NAAGA treatment (80.8% of the cases). Clinical and functional signs disappeared without recourse to corticoids.. In the moderate forms of seasonal and intra-annual allergic conjunctivitis, NAAGA treatment alone is sufficient. The association with Levocabastine is necessary only in cases of highly bothersome functional signs. The use of corticoids should be reserved for the serious forms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Child; Child, Preschool; Clinical Protocols; Conjunctivitis, Allergic; Dipeptides; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Seasons; Young Adult

This comparative and randomised pilot study assessed the clinical and biological efficacy of Naaxia Sine(R) eye-drops versus levocabastine eye-drops in the treatment of vernal keratoconjunctivitis (VKC).. Twenty-three VKC patients were randomised and treated bilaterally for 28 days with N-acetyl-aspartyl-glutamate (NAAGA) or levocabastine (LEVO) eye-drops. The primary efficacy variable, overall evolution of eosinophil cationic protein (ECP) tear concentrations, was assessed in a masked fashion on D0, D7 and D28. Clinical symptoms and signs were reported at the same time points. Biological parameters were analysed with a non-parametric rank-based approach. Global tolerance was assessed by the investigator and patient.. At all time points, ECP tear levels were significantly reduced in the NAAGA compared with the LEVO group (p = 0.023). Reduction of eosinophil leucocytes and tear lymphocytes was higher not significant in the NAAGA group. The same trend was observed for the evolution of total ocular symptom score. There were no significant differences between treatment groups in the occurrence of adverse effects, except for burning which was more frequent in the LEVO group (p = 0.002).. The anti-eosinophilic actions of NAAGA were shown by a significant reduction of ECP tear concentrations. A decreased lymphocyte count and an overall improvement of the symptomatology were also noted. Moreover, the tolerability of NAAGA appeared to be better.

Topics: Anti-Inflammatory Agents; Child; Conjunctivitis, Allergic; Dipeptides; Eosinophil Cationic Protein; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Lymphocyte Count; Male; Ophthalmic Solutions; Osmolar Concentration; Pilot Projects; Piperidines; Preservatives, Pharmaceutical; Tears; Treatment Outcome

Recent decades have been marked by an increasing number of patients suffering from ocular allergic-like symptoms without being associated with an increase in IgE levels. These symptoms include heaviness of the lid, foreign body sensation, burning, stinging and photophobia. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between allergic-like symptoms and environmental factors such as outdoor air pollutants or poor indoor air quality. An ocular surface subclinical inflammation is thought to be responsible for pseudoallergic, pollution-related conjunctivitis. The complement system is considered as one of the major effector mechanisms involved in initiation of the subclinical inflammation that leads to IgE-independent eye irritation.. To study the capability of nine antiallergic eyedrops commonly used in the treatment of allergic conjunctivitis to inhibit complement activation induced in vitro by pollutants.. Normal human serum obtained from healthy individuals was used as a source of complement. Activation of complement was assessed using the complement hemolytic 50% (CH50) assay, in the absence or the presence of antiallergic eyedrops and in the absence or the presence of various stimuli, including sand, common house dust, eye mascara, and Dactylis glomerata pollen extract. Zymosan was used as a standardized complement activator. The following eyedrops were studied: Naabak (4.9% N-acetyl aspartic acid-glutamic acid, NAAGA, sodium salt), Almide (lodoxamide 0.1%), Levophta (0.05% levocabastine), Emadine (0.05% emedastine), Tilavist (2% nedocromil), Allergodil (0.05% azelastine), Patanol (olopatadine), and Zaditen (0.025% ketotifen). Effects of preservative-free lodoxamide and ketotifen were also assessed and compared to those of the preserved formulations. A solution of 0.01% benzalkonium chloride (BAC), the most widely used preservative in topical eyedrops, was also tested.. Zymosan-induced activation of complement (30+/-6%) was significantly lowered by preincubation of serum with unpreserved NAAGA (16.6+/-4%, p=0.0026) or benzalkonium-preserved nedocromil (20+/-2%, p=0.022). Preserved levocabastine, emedastine, olopatadine and ketotifen did not interfere with zymosan-induced complement activation, whereas preserved azelastine, lodoxamide and benzalkonium chloride significantly aggravated complement activation induced by zymosan. Similar results were obtained when complement activation was triggered by sand, common house dust, mascara, or by an allergenic extract of Dactylis glomerata pollen. In the absence of complement activator, none of the antiallergic eyedrops induced a significant change in CH50 titer, indicating that the deleterious pro-inflammatory effect of preserved azelastine and lodoxamide may occur only once complement activation has been initiated, i.e., on an inflamed ocular surface.. Among the antiallergic eyedrops tested in this study, only Naabak and Tilavist were found to significantly inhibit complement activation triggered by particulate matters or pollen allergenic extract. Such an anticomplement activity confers these two molecules a potential in the therapeutic management of pollution-related pseudoallergic conjunctivitis.

Topics: Air Pollutants; Anti-Allergic Agents; Benzalkonium Compounds; Benzimidazoles; Complement Activation; Conjunctivitis; Cosmetics; Dibenzoxepins; Dipeptides; Drug Evaluation; Dust; Humans; In Vitro Techniques; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Ophthalmic Solutions; Oxamic Acid; Phthalazines; Piperidines; Pollen; Silicon Dioxide; Zymosan

Leukocytes from ten allergic patients (five allergic to dust-mites and five allergic to pollen) were treated with N-acetyl aspartyl glutamic acid (NAAGA) 4.9%, disodium cromoglycate (DSCG) 2%, lodoxamide (LODO) 1%, and levocabastine (LEVO) 0.5% (concentrations representing the pharmaceutical eyedrop preparations) for 20 minutes. Degranulation was then induced with Complement (rHu5Ca). Histamine was measured in the supernatant with ELISA. LODO and LEVO were inactive in blocking histamine released from human cells, and paradoxical unexpected effects were found with these two agents. They both induced significant histamine release in almost 100% of the samples. DSCG was able to block histamine release in seven patients out of nine (ranging between 5 and 34%). NAAGA was the most active agent on human cells and was able to block basophil degranulation in nine patients out of nine (inhibition ranging between 4 and 66% of total histamine pool).

Topics: Allergens; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Basophil Degranulation Test; Basophils; Cell Degranulation; Complement C5; Cromolyn Sodium; Dipeptides; Enzyme-Linked Immunosorbent Assay; Histamine; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity, Immediate; Ophthalmic Solutions; Oxamic Acid; Piperidines; Recombinant Proteins