Background Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergic diseases nor the characteristics of these DNA traps have been studied. Objective We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps. Methods Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis (ECRS) and eosinophilic otitis media (EOM) were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by fluorescence microscopy. Results Abundant nuclear histone H1-bearing DNA traps had formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro, following brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and by hydrophobic interactions microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA traps ultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely due to the lesser protease activities of eosinophils. Conclusions In human allergic diseases, the local cytolysis of eosinophils not only releases free eosinophil granules but also generates nuclear-derived DNA traps that are major extracellular structural components within eosinophil-rich secretions.

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Production of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma.

Antigens that produce an antibody response in some members of a species may fail to do so in others. The response to an antigen is controlled by a gene termed the immune response (Ir) gene, which is transmitted as a single dominant trait. We have provided evidence for similar immune suppression (Is) genes which control non-responsiveness through the antigen specific suppressor T cell. The non-responsiveness is also dominantly inherited and the Is genes are linked to the histocompatibility (HLA) antigen system. Here we report that the HLA-DR2 molecule from a non-responder haplotype (HLA-Dw12-DR2-DQwl) is required for the proliferative T cell response to schistosoma japonicum (Sj) antigen, as a restriction element, indicating that the HLA-DR2 is the product of the Ir gene, and that the HLA-DQwl molecule of the non-responder haplotype is important in the antigen-specific suppression of the response to this antigen, suggesting that it is the product of the Is gene. We therefore conclude that the HLA-DR and DQ molecules, which are controlled by the distinct genes in the MHC multigene family, regulate immune response and immune suppression and that the gene for HLA-DQ is epistatic to that for HLA-DR in controlling the immune response to schistosomal antigen in humans.

Intracystic injection of OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a treatment of first choice for this disease. We tried this therapy in 32 patients with ranula (oral floor type in 21 cases and plunging type in 11 cases). Disappearance or marked reduction of the lesion was observed in 31 patients (97%) who had this therapy, and local scarring did not occur in any patient. As side effects, local pain at the injection site and fever (37 degrees C to 39 degrees C) were observed in almost half of the patients who had this therapy, but such problems resolved within a few days. We treated the initial 4 cases in the hospital for 4 to 5 days, but after the safety of this method had been confirmed, we treated the other 28 cases on an outpatient basis. Thus, we confirmed that intracystic injection therapy with OK-432 is relatively safe and can be used as a substitute for surgery in the treatment of ranulas.

SummaryWe used a rapid, visually read, field applicable monoclonal antibody (MoAb)-dipstick assay for specific diagnosis of urinary schistosomiasis together with microscopy to determine the prevalence of infant schistosomiasis in a community in the Awutu-Efutu Senya District in the Central Region of Ghana.The study group consisted of 97 infants (51 males and 46 females) aged 2 months to 5 years. A total of 75 of 97 (77.3%) subjects submitted stool samples; none had Schistosoma mansoni. Three individuals (3.1%) had hookworms but there were no other intestinal helminths. The urinary schistosomiasis prevalence by MoAb-dipstick (30%) was higher (P < 0.05) than that estimated by microscopy (11.2%). However, three of nine (33.3%) microscopically confirmed cases tested MoAb-dipstick positive after pre-treatment of the urine specimen with heat. The youngest infant to be found infected with S. haematobium microscopically was 4 months old. Fifteen of 71 S. haematobium egg negative individuals tested dipstick positive, giving a dipstick specificity of 78.9% as compared with microscopy as gold standard test. The relative sensitivity of the dipstick was 100%.

The ground dried rhizome of the plant, Curcuma longa LINN has long been used as a naturally occurring medicine for the treatment of inflammatory and other diseases, and has also been used as a coloring agent and spice in many foods. 1)The powdered rhizome is commonly called turmeric. Curcumin (diferuloylmethane) is a major active ingredient that has been identified as the major pigment in turmeric. Curcumin is well known as a potent anti-oxidant, 2,3) and recent studies have revealed that it is a potent inhibitor of reactive oxygen-generating enzymes, such as lipoxygenase/cyclooxygenase, 4,5) xanthine dehydrogenase/oxidase 6) and inducible nitric oxide synthase 7) and it possesses anti-inflammatory activity. 8,9) Moreover, it has shown anti-carcinogenic activity in animal models, such as colon tumor initiation by azoxymethane 10) and skin tumor promotion induced by phorbol ester TPA.11) Recently, curcumin has been considered by oncologists as a potential third generation cancer chemopreventive agent, and clinical trials using it have been carried out in several laboratories.Leishmania such as Leishmania major are the protozoan parasite responsible for leishmaniasis. So far, medicines used for the treatment of leishmaniasis such as pentavalent antimonials and pentamidine are toxic or have severe side effects, for example renal, cardiac and neural toxicity, shock and risk of diabetes.12) Other medicines such as amphotericin B are restricted to hospital use. In addition, resistance towards these medicines have been observed. 13) Thus, the development of a new agent is urgently needed.During the search for the candidate of anti-parasitic agents from natural resources, we have found that curcumin has leishmanicidal activity in vitro. MATERIALS AND METHODSChemicals Curcumin was purchased from Funakoshi Co., Ltd. (Tokyo, Japan) and other chemicals used were special grade.Axenic Cultivation of Leishmania The medium used for the cultivation of promastigotes of L. major (MHOM/ SU/73/5ASKH) was SDM-79, previously described by Brun and Schonenberger.14) Leishmania were cultured into 25 cm 2 -tissue culture flasks containing 5 ml of culture medium per flask and maintained therein at 27°C in an atmosphere of 5% CO 2 -95% air.Leishmanicidal Assay Cultured leishmania of promastigotes were centrifuged at 600 g for 5 min at 4°C, and the parasites then resuspended with culture medium, diluted to a density of 5ϫ10 5 /ml and inoculated into 96-well plate. The medium (0.1 ml) containing various concentrations of curcumin dissolved in dimethyl sulfoxide (DMSO) was added into each well and incubated at 27°C in an atmosphere of 5% CO 2 -95% air. The final concentration of DMSO was 0.5%. After incubation for an appropriate period, the number of surviving leishmania was determined microscopically by counting in a Burker-Turk hemocytometer. The leishmanicidal activity of curcumin was shown as 50% growth inhibitory concentration (GI 50 ), 100% growth inhibitory concentration (TGI) and LD 50 after incubation with leishmania for 24 h. 100% gr...

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