Development of a nondestructive leak testing method utilizing the head space analyzer for ampoule products containing ethanol-based solutions.

The application of a head space analyzer for oxygen concentration was examined to develop a novel ampoule leak test method. Studies using ampoules filled with ethanol-based solution and with nitrogen in the headspace demonstrated that the head space analysis (HSA) method showed sufficient sensitivity in detecting an ampoule crack. The proposed method is the use of HSA in conjunction with the pretreatment of an overpressurising process known as bombing to facilitate the oxygen flow through the crack in the ampoule. The method was examined in comparative studies with a conventional dye ingress method, and the results showed that the HSA method exhibits sensitivity superior to the dye method. The results indicate that the HSA method in combination with the bombing treatment provides potential application as a leak test for the detection of container defects not only for ampoule products with ethanol-based solutions, but also for testing lyophilized products in vials with nitrogen in the head space. LAY ABSTRACT: The application of a head space analyzer for oxygen concentration was examined to develop a novel ampoule leak test method. The proposed method is the use of head space analysis (HSA) in conjunction with the pretreatment of an overpressurising process known as bombing to facilitate oxygen flow through the crack in the ampoule for use in routine production. The result of the comparative study with a conventional dye leak test method indicates that the HSA method in combination with the bombing treatment can be used as a leak test method, enabling detection of container defects.

Neuroselective transcutaneous electrical stimulation reveals neuronal sensitization in atopic dermatitis.

BACKGROUND: The neuroselective transcutaneous electrical stimulator (NTES) can provoke itch and/or pain by the application of a 5-Hz alternating current. OBJECTIVE: We sought to examine whether there is any difference in the perception of the stimulus evoked by the NTES between patients with atopic dermatitis (AD) and healthy control subjects. METHODS: In all, 24 healthy control subjects and 24 patients with AD (nonlesional skin) were stimulated on 7 body sites using the NTES. Qualitative differences in the evoked perceptions and quantitative differences in the current intensity required to evoke perception were statistically analyzed. RESULTS: The NTES preferentially evoked itch in patients with AD. The current perception threshold was statistically lower in AD than in healthy control subjects on 3 body sites. LIMITATIONS: Tests were performed on limited body areas. CONCLUSION: We demonstrated that the NTES can reveal neuronal sensitization to itch in nonlesional atopic skin.

Neuroselective transcutaneous electric stimulation reveals body area-specific differences in itch perception.

BACKGROUND: Electrically evoked itch has been reported, although the electrodes, the frequency, and the pulse duration used were not standardized. OBJECTIVE: To examine whether a neuroselective transcutaneous electrical stimulator (NTES; Neurometer; Neurotron, Inc, Baltimore, Md) can evoke itch and whether it can provoke itch on any body area. METHODS: Twelve healthy subjects were stimulated on 30 body sites by 5 Hz alternating current produced by the NTES. We classified the evoked perceptions into two sensations (with and without itch) and divided the examined sites into 7 groups: G1, head and neck; G2, arm; G3, palm; G4, the dorsal surface of the hand; G5, knee and leg; G6, dorsal foot; and G7, ankle. The data were then statistically analyzed. RESULTS: The NTES preferentially evoked itch at the G4 and G7 sites, and a sensation without itch at the G1 site. LIMITATION: Tests were performed on limited body areas. CONCLUSION: The NTES can provoke itch, it was discovered that there are body area-specific differences in itch sensation.

Synthesis, characterization, and detailed electrochemistry of binuclear ruthenium(III) complexes bridged by bisacetylacetonate. Crystal and molecular structures of [[Ru(acac)2]2(tae)] (acac = 2,4-pentanedionate ion, tae = 1,1,2,2-tetraacetylethanate dianion).

Binuclear beta-diketonatoruthenium(III) complexes [[Ru(acac)(2)](2)(tae)], [[Ru(phpa)(2)](2)(tae)], and [(acac)(2)Ru(tae)Ru(phpa)(2)] and binuclear and mononuclear bipyridine complexes [[Ru(bpy)(2)](2)(tae)](PF(6))(2) and [Ru(bpy)(2)(Htae)]PF(6) (acac = 2,4-pentanedionate ion, phpa = 2,2,6,6-tetramethyl-3,5-heptanedionate ion, tae = 1,1,2,2-tetraacetylethanate dianion, and bpy = 2,2'-bipyridine) were synthesized. The new complexes have been characterized by (1)H NMR, MS, and electronic spectral data. Crystal and molecular structures of [[Ru(acac)(2)](2)(tae)] have been solved by single-crystal X-ray diffraction studies. Crystal data for the meso isomer of [[Ru(acac)(2)](2)(tae)] have been confirmed by the dihedral angle result that two acetylacetone units of the bridging tae ligand are almost perpendicular to one another. A detailed investigation on the electrochemistry of the binuclear complexes has been carried out. The electrochemical behavior details of the binuclear complexes have been compared with those of the mononuclear complexes obtained from the half-structures of the corresponding binuclear complexes. Studies on the effects of solvents on the mixed-valence states of Ru(II)-Ru(III) and Ru(III)-Ru(IV) complexes have been carried out by various voltammetric and electrospectroscopic techniques. A correlation between the comproportionation constant (K(c)) and the donor number of the solvent has been obtained. The K(c) values for the binuclear complexes have been found to be low because of the fact that two acetylacetone units of the bridging tae ligand are not in the same plane, as revealed by the crystal structure of [[Ru(acac)(2)](2)(tae)].

Properties of olopatadine hydrochloride, a new antiallergic/antihistaminic drug.

Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that is a selective histamine H1 receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritus, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.

Evaluation of the efficacy of antihistamines using human monocyte-derived dendritic cells stimulated with histamine.

BACKGROUND: It has been reported that histamine induces CD86 expression and chemokine production in human immature monocyte-derived dendritic cells (MoDCs), which can be blocked by both H(1)- and H(2)-receptor antagonists. OBJECTIVE: We sought to examine whether the efficacy of H(1)-type antihistamines can be assessed by using MoDCs. METHODS: We examined the suppressive effects of 1 H(2)-type antihistamine (cimetidine) and 5 different H(1)-type antihistamines (cetirizine, diphenhydramine, ketotifen, olopatadine, and emedastine) on the induction of CD86 and IL-8 production by MoDCs from 23 healthy individuals stimulated with histamine. We also examined the responses of MoDCs from 13 patients with chronic urticaria to these antihistamines, and compared the in vitro efficacy with the actual clinical response to antihistamines evaluated by patient and physician assessments. RESULTS: All the antihistamines we examined suppressed the increase of CD86(+) cells after histamine stimulation in a dose-dependent fashion, and all H(1)-type antihistamines were more efficacious than cimetidine. IL-8 production stimulated with histamine was also suppressed by cetirizine, ketotifen, and olopatadine. Unexpectedly, the suppressive effect of these antihistamines on the CD86 augmentation was highly variable among different healthy control participants. Interestingly, in 10 of 13 cases of chronic urticaria, this in vitro analysis of antihistamines correlated with the clinical response to antihistamines. CONCLUSION: This study suggests that the evaluation of antihistamines using MoDCs can be a useful method for the screening of effective antihistamines, for the comparison of the efficacy of antihistamines, and for predicting the efficacy of antihistamines on an individual basis.