RESUMO
BACKGROUND: There have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. METHODS: This was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. RESULTS: The percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. CONCLUSIONS: Dual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses.
Assuntos
Rinite Alérgica/tratamento farmacológico , Imunoterapia Sublingual/efeitos adversos , Imunoterapia Sublingual/métodos , Adolescente , Adulto , Animais , Antígenos de Dermatophagoides/administração & dosagem , Criança , Cryptomeria/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Pyroglyphidae/imunologia , Rinite Alérgica/etiologia , Comprimidos , Adulto JovemRESUMO
A new high performance liquid chromatography (HPLC) method has been established for quantitative and qualitative analysis of three tetracyclic iridoids: ML-2-3 (1), molucidin (2), and ML-F52 (3), which are responsible for anti-trypanosomal and anti-leishmanial activities of Morinda lucida Bentham leaves. Separation of 1-3 from dried 80% aqueous (aq.) ethanol extract was achieved on a reversed-phase cholester column packed with cholesteryl-bonded silica using an acetonitrile-0.1% aq. formic acid mobile phase system. Ultraviolet-visible (UV-VIS) spectroscopy was employed for detection of compounds, and their contents were determined by measuring absorbance at 254 nm. Depending on the above system, several factors potentially affecting the concentration of tetracyclic iridoids were evaluated resulting in several variation on plant organs, seasonality, variation between individual trees, and branch positions within the trees. Moreover, we developed a simple, quick, and effective method for tetracyclic iridoid isolation from M. lucida leaves that consisted of extraction by sonication into 80% aq. ethanol, basic hydrolysis, acid neutralization, liquid-liquid extraction into an organic solvent, and reverse phase open column chromatography. Employing this method, we have succeeded to obtain 1 as a colorless crystal yielding of 0.23%, which was 28 times higher than that of previous isolation method. Setting up methodology in this paper may be important for future in vitro and in vivo studies of tetracyclic iridoids and moreover for their applications in new drug design and development.
Assuntos
Fracionamento Químico/métodos , Iridoides/farmacologia , Morinda/química , Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , Fracionamento Químico/instrumentação , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Desenho de Fármacos , Iridoides/análise , Iridoides/química , Iridoides/isolamento & purificação , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/química , Pesquisa Qualitativa , Solventes/química , Tripanossomicidas/análise , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação , Trypanosoma/efeitos dos fármacosRESUMO
BACKGROUND: It past 4 years in 2018 after the first treatment of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. The purpose of this study is to clear the clinical efficacy of SLIT in a large amount of pollen dispersal in 2018 (total 5041 grain). METHODS: The subjects were 270 SLIT (83 forth year of treatment, 72 third year, 48 second year, 67 first year), 320 primary pharmacotherapy that started therapies before pollen dispersal, and 424 untreated. The clinical efficacy was evaluated with symptom scores of Japanese rhinoconjuctivitis quality of life questionnaire No1, medication scores and combined total nasal symptom-medication scores, and visual analog scale of nose, eye and total symptoms. RESULTS: Each SLIT was significantly better than untreated in all assessments, and better than primary pharmacotherapy in assessments of total symptom. SLITs of third and forth year of treatment were also better than primary pharmacotherapy in nasal symptoms. SLIT patients, whose symptom scores of nose and eye were 0 and 1 point without any rescue drugs, accounted for 41.0%, 31.9%, 18.8%, 20.9% in the order from the fourth year to the first year. Of them, patients with score 0 occupied 12.0%, 12.5%, 4.2%, 4.5%, in order. There was no patient who needs treatments for adverse events. CONCLUSION: SLIT was significantly effective compared with primary pharmacotherapy or untreated group in a large amount of pollen dispersal. It was better to treat at least for 4 years.
Assuntos
Hipersensibilidade/terapia , Pólen , Imunoterapia Sublingual , Administração Sublingual , Alérgenos , Humanos , Qualidade de Vida , Resultado do TratamentoRESUMO
Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti-Trypanosoma, anti-Leishmania, and anti-Plasmodium activities in vitro and investigated their mechanisms of action. Twenty-three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC50 values less than 20 µg/ml. Eleven extracts showed high anti-Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC50 (selectivity index [SI]) values were 5.51 µg/ml (35.00) and 5.96 µg/ml (13.09), respectively. Nine extracts had high anti-Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC50 (SI) values were 10.8 µg/ml (1.50) and 10.1 µg/ml (0.37), respectively. Six extracts had high anti-Plasmodium activity with the leaf and stem-bark extracts of Terminalia ivorensis recording the highest activity. Their IC50 (SI) values were 7.26 µg/ml (129.36) and 17.45 µg/ml (17.17), respectively. Only M. lucida at 25 µg/ml induced significant apoptosis-like cell death in Trypanosoma parasites. Anti-Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.
Assuntos
Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plasmodium/efeitos dos fármacos , Trypanosoma/efeitos dos fármacos , Apoptose , Gana , Humanos , Células JurkatRESUMO
It past 3 years in 2017 after the first purchase of the drug for sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). We reported the clinical efficacy of SLIT in the first and the second treated year. PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT in the third treated year by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy. METHODS: We compared the clinical efficacy in 2017, of 112 SLIT in the third treated year with 38 SCIT, 364 primary pharmacotherapy that started therapies before pollen dispersal, 254 pharmacotherapy that started therapies after pollen disposal, or 333 non-treatment. The clinical efficacy was evaluated with symptom scores, total nasal symptom scores and combined total nasal symptom-medication scores (TNSMS), symptoms of nose and eye by visual analog scale (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1). RESULTS: Both SCIT and SLIT showed good clinical efficacy without significant difference in every assessment. Both SCIT and SLIT were significantly better than other pharmacotherapy in most assessment. Patients, whose symptom scores of nose and eye were 0 and 1 point without any rescue drugs, accounted for 9 and 24% of total SLIT, respectively. CONCLUSION: SLIT in the third treated year showed good clinical efficacy in reducing symptoms and TNSMS of JCP, and in improving QOL. SLIT was significantly effective compared with other pharmacotherapies.
Assuntos
Cryptomeria/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Administração Sublingual , Adulto , Feminino , Humanos , Masculino , Rinite Alérgica Sazonal/imunologia , Imunoterapia Sublingual/efeitos adversos , Fatores de TempoRESUMO
Sublingual immunotherapy (SLIT) is thought to have enhanced efficacy in the second year of treatment. We studied treatment efficacy in both the first and the second years of treatment (2015 and 2016, respectively) in patients who began SLIT in 2014. Methods: We compared 132 patients who underwent SLIT (age, 41.8 ± 17.5 years; male-to-female ratio, 75: 57) and a control group of 56 patients who underwent primary pharmacotherapy (age, 44.9 ± 13.5 years; male-to-female ratio, 25: 31). The study was performed during the peak pollen seasons of 2015 and 2016. Pollen dispersal was similar in 2015 and 2016 (2,509 grains/cm2 and 3,505 grains/cm2, respectively). The clinical efficacy of SLIT was evaluated by assessing nasal and eye symptoms and total symptoms with symptom scores and combined symptom-medication scores, visual analog scale scores, and quality of life (QOL) scores according to the Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No. 1). QOL was also evaluated with JRQLQ No. 1. The first endpoint was enhanced efficacy of SLIT in the second year compared with that in the first year. Results: With respect to nasal and eye symptoms, the assessments in the primary pharmacotherapy group were unchanged in the second year; however, most of these assessments in the SLIT group demonstrated significantly enhanced efficacy of SLIT in the second year. In QOL of SLIT, only 2 of 17 showed significantly enhanced efficacy of SLIT in the second year. Conclusion: SLIT shows enhanced efficacy in the second year.
Assuntos
Cryptomeria/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Administração Sublingual , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica Sazonal/imunologia , Estações do Ano , Inquéritos e Questionários , Adulto JovemRESUMO
It past 2 years in 2016 after the first purchase of the drug for sublingual immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). PURPOSE: The purpose of this study is to clear the clinical efficacy of SLIT in the second treated year by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or other pharmacotherapy. METHODS: We started SLIT at our clinic in October-December, 2014. We compared the clinical efficacy in 2016, of 133 SLIT with 46 SCIT, 351 primary pharmacotherapy that started therapies before pollen dispersal, 221 pharmacotherapy that started therapies after pollen disposal, or 337 non-treatment. The clinical efficacy was evaluated with symptom scores and combined symptom-medication scores (SMS), symptoms of nose and eye by visual analog scale (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ No1). RESULTS: Fourteen cases by unknown reasons and 3 cases by inevitable reasons were dropped out for 2 years. Both SCIT and SLIT showed good clinical efficacy without significant difference in every assessment. Both SCIT and SLIT were significantly better than other pharmacotherapy in most assessment. Patients, whose symptom scores of nose and eye were 0 or 1 point without any rescue drugs, accounted for 26.3% of total SLIT. CONCLUSION: SLIT in the second treated year showed good clinical efficacy in reducing symptoms and SMS of JCP, and in improving QOL. SLIT was significantly effective compaired with other pharmacotherapies.
Assuntos
Cryptomeria/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Adulto , Feminino , Humanos , Masculino , Qualidade de Vida , Rinite Alérgica Sazonal/imunologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Previous publications suggest that nutritional supplements have anti-trypanosome activity in vitro, although apparent efficacy was not noted in vivo. This study was conducted by experimentally infecting mice with Trypanosoma brucei brucei to assess the anti-trypanosome activity of various nutritional supplements with the hope of finding possible application in the treatment of African trypanosomiasis. METHODS: Activities of nutritional supplements were screened in vitro against bloodstream forms of T. b. brucei. To evaluate selectivity, we used two mammalian cells, Jurkat cells and Vero cells. The IC50 values and selectivity index values were calculated, and supplements with promising efficacy in vitro were selected for further testing in vivo. Mice were infected intraperitoneally with 1 × 10(3) T. b. brucei. We observed parameters for disease progression such as parasitemia, red blood cell count, white blood cell count, survivability, and splenomegaly. Morphological profiles after the treatment were analyzed by scanning electron microscopy. RESULTS: Vitamin D3 showed anti-trypanosome efficacies both in vitro and in vivo. It seemed to have suppressive effects on parasitemia, and spleen weight was also significantly lower in vitamin D3-treated mice when compared to non-treated control mice. There was, however, no significant prolonged survivability of infected mice treated with vitamin D3. Among green tea extracts, polyphenon-60 and epigallocatechin gallate had suppressive effects against T. b. brucei in vitro, but in vivo efficacies were marginal. CONCLUSIONS: Treatment with nutritional supplements, vitamin D3, and polyphenon-60 seemed to have anti-trypanosome activity in vitro and protective activity to some extent in vivo, respectively, although those supplements themselves did not have curable effects. The exact mechanisms of action are not clear, but the significant efficacy in vitro suggested direct effects of supplements against African trypanosome parasites.
RESUMO
Trypanosoma brucei parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide. Morinda lucida Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl3 fraction of M. lucida leaves, which possess activity against the GUTat 3.1 strain of T. brucei brucei The 50% inhibitory concentrations (IC50) of molucidin, ML-2-3, and ML-F52 were 1.27 µM, 3.75 µM, and 0.43 µM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of Trypanosoma parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.
Assuntos
Antiprotozoários/farmacologia , Iridoides/farmacologia , Morinda/química , Plantas Medicinais/química , Tripanossomicidas/farmacologia , Animais , Antiprotozoários/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Iridoides/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Tripanossomicidas/química , Trypanosoma/efeitos dos fármacos , Trypanosoma/patogenicidade , Tripanossomíase Africana/fisiopatologiaRESUMO
Sublingual immunotherapy (SLIT) for Japanese cedar pollinosis is known to be effective. However, better SLIT adherence is needed to improve its safety and efficacy. ãPurpose: The purpose of this study was to evaluate SLIT adherence and its influence on clinical outcome. ãMethods: We conducted a detailed survey of 132 patients who have been receiving SLIT for 2 years on adherence at each visit using both questionnaires and direct calculation from prescription. Questionnaires on total symptoms using the visual analog scale (VAS), face scale, and total nasal symptom medication score (TNSMS) were obtained at the peak season for Japanese cedar pollinosis. ãResults: Good adherence by prescription for 2 years was observed in 83.1% ± 11.7% of patients. The adherence in the second year (80.8% ± 13.6%) was lower than that in the first year (88.5% ± 9.8%). However, adherence by questionnaire was 13.5% higher than that by prescription. VAS of total symptoms and adherence did not correlate; however, evaluations by VAS, face scale, and TNSMS were significantly improved if the adherence cut-off value was set to 70% or 75%. ãConclusion: Our results suggest that SLIT adherence for Japanese cedar pollinosis is high and adequate adherence is required for better efficacy.
Assuntos
Cryptomeria/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Administração Sublingual , Adulto , Idoso , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Rinite Alérgica Sazonal/imunologia , Resultado do TratamentoRESUMO
Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious health problem in many African countries with thousands of new infected cases annually. Chemotherapy, which is the main form of control against HAT has been characterized lately by the viewpoints of toxicity and drug resistance issues. Recently, there have been a lot of emphases on the use of medicinal plants world-wide. Morinda lucida Benth. is one of the most popular medicinal plants widely distributed in Africa and several groups have reported on its anti-protozoa activities. In this study, we have isolated one novel tetracyclic iridoid, named as molucidin, from the CHCl3 fraction of the M. lucida leaves by bioassay-guided fractionation and purification. Molucidin was structurally elucidated by (1)H and (13)C NMR including HMQC, HMBC, H-H COSY and NOESY resulting in tetracyclic iridoid skeleton, and its absolute configuration was determined. We have further demonstrated that molucidin presented a strong anti-trypanosomal activity, indicating an IC50 value of 1.27 µM. The cytotoxicity study using human normal and cancer cell lines indicated that molucidin exhibited selectivity index (SI) against two normal fibroblasts greater than 4.73. Furthermore, structure-activity relationship (SAR) study was undertaken with molucidin and oregonin, which is identical to anti-trypanosomal active components of Alnus japonica. Overlapping analysis of the lowest energy conformation of molucidin with oregonin suggested a certain similarities of aromatic rings of both oregonin and molucidin. These results contribute to the future drug design studies for HAT.
Assuntos
Iridoides/química , Iridoides/farmacologia , Morinda/química , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Animais , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Iridoides/isolamento & purificação , Modelos Moleculares , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Tripanossomíase Africana/tratamento farmacológicoRESUMO
The crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Subsequent chromatographic separation resulted in the isolation of two novel diarylheptanoids, known as alnuside C (2) and alnuside D (3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-ß-D-glucopyranoside (1), oregonin (4) and hirsutanone (5). The structures of the isolates were elucidated based on the use of extensive spectroscopic and chemical methods. Among the isolated diarylheptanoids, oregonin (4) (a major component of plant bark) and hirsutanone (5) exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC50 values of 1.14 and 1.78 µM, respectively. We confirmed that oregonin (4) and hirsutanone (5) were not toxic to human normal skin fibroblast cells (NB1RGB) and colon cancer cells (HCT-15) at a concentration of 50 µM; however, lower levels of toxicity were observed for leukemia cells. To determine the structure activity relationships of the isolated components, we performed Conformation Search and found that the 3-oxo function of the heptane chain in the diarylheptanoid molecule is required for their trypanocidal activity.
Assuntos
Alnus , Diarileptanoides/farmacologia , Extratos Vegetais/farmacologia , Tripanossomicidas , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei brucei/crescimento & desenvolvimento , Animais , Células Cultivadas , Neoplasias do Colo/patologia , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Leucemia/patologia , Casca de Planta , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Pele/citologia , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
BACKGROUND: This study intended to assess the severity of Japanese cedar pollinosis using the Practical Guideline for the Management of Allergic Rhinitis in Japan (PG-MARJ) and the Allergic Rhinitis and its Impact on Asthma (ARIA) Guideline. METHODS: An Internet questionnaire survey of patients with pollinosis was conducted in mid-May 2011 and responses were obtained from 3382 individuals who had potential symptoms of Japanese cedar pollinosis from February to early May 2011 and who had experienced such symptoms for at least two pollen seasons. RESULTS: According to PG-MARJ, 23.5% of the respondents had severest rhinitis, 29.4% severe rhinitis, 31.3% moderate rhinitis, 13.8% mild rhinitis and 2.0% asymptomatic rhinitis. According to ARIA, 67.2% of them had moderate/severe persistent rhinitis, 23.8% moderate/severe intermittent rhinitis, 4.4% mild persistent rhinitis and 4.6% mild intermittent rhinitis. CONCLUSIONS: Moderate to severe rhinitis was diagnosed in more than 80% of the respondents according to PG-MARJ, while moderate/severe rhinitis was diagnosed in more than 90% of the respondents according to ARIA. Most of the respondents suffered relatively severe pollinosis. More than 80% of the respondents had all the three major symptoms (i.e., sneezing, rhinorrhea and nasal blockage). Disagreement in the severity assessment between the two guidelines was noted in approximately 20% of the respondents.
Assuntos
Alérgenos/imunologia , Cryptomeria/efeitos adversos , Pólen/efeitos adversos , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/fisiopatologia , Alérgenos/efeitos adversos , Cryptomeria/imunologia , Feminino , Inquéritos Epidemiológicos , Humanos , Japão , Masculino , Pólen/imunologia , Guias de Prática Clínica como Assunto , Rinite Alérgica Sazonal/etiologia , Rinite Alérgica Sazonal/terapia , Estações do Ano , Índice de Gravidade de DoençaRESUMO
An effective malaria vaccine is a public health priority. Proteins expressed during the blood-stage of the parasite life cycle have been proposed as good vaccine candidates. No such blood-stage vaccine, however, is available against Plasmodium falciparum, the deadliest Plasmodium species. We show here that P. falciparum serine repeat antigen 5 (SERA5) is a potential vaccine immunogen. We have constructed a new recombinant molecule of SERA5, namely SE36, based on previously reported SE47' molecule by removing the serine repeats. Epidemiological study in the holo-endemic population of Solomon Islands shows highly significant correlation of sero-conversion and malaria protective immunity against this antigen. Animal experiments using non-human primates, and a human phase 1a clinical trial assessed SE36 vaccine immunogenicity. Vaccination of squirrel monkeys with SE36 protein and aluminum hydroxyl gel (SE36/AHG) conferred protection against high parasitemia and boosted serum anti-SE36 IgG after P. falciparum parasite challenge. SE36/AHG was highly immunogenic in chimpanzees, where serum anti-SE36 IgG titers last more than one year. Phase 1a clinical trial (current controlled trials, ISRCTN78679862) demonstrated the safety and immunogenicity of SE36/AHG with 30 healthy adults and 10 placebo controls. Three subcutaneous administrations of 50 and 100microg dose of SE36/AHG were well-tolerated, with no severe adverse events; and resulted in 100% sero-conversion in both dose arms. The current research results for SE36/AHG provide initial clinical validation for future trials and suggest clues/strategies for further vaccine development.
Assuntos
Antígenos de Protozoários/imunologia , Imunoglobulina G/sangue , Vacinas Antimaláricas/imunologia , Malária Falciparum/parasitologia , Parasitemia/prevenção & controle , Adulto , Animais , Antígenos de Protozoários/genética , Avaliação Pré-Clínica de Medicamentos , Humanos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/genética , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Melanesia/epidemiologia , Parasitemia/epidemiologia , Parasitemia/parasitologia , Plasmodium falciparum/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Saimiri , Resultado do Tratamento , VacinaçãoRESUMO
BACKGROUND: Japanese cedars and grass are famous for causing pollen allergy with antigen. But recently, many other antigens causing pollen allergy are coming to the front. We investigated positive ratios of pollen antigens of the consultation patients. METHODS: 151 subjects (90 males and 61 females) were examined for allergic reactions by a scratch test. We used Yasueda's method to take pollen extracts. RESULTS: A positive ratio of Cocksfoot (Dactylis glomerata) (51%) was higher than that of cedar (Cryptomeria japonica) (45%). Each positive ratio of birch (Betula platyphylla var. japonica), walnut (Juglans mandshurica), sheep sorrel (Rumex acetosella), oak (Quercus serrata) and willow (Salix spp.) was 13%, 8%, 9%, 11%, 10%, respectively. These were lower than that of Cocksfoot or cedar, but higher than that of Fungi: Alternaria, Candida and Aspergillus. CONCLUSION: Grass (Gramineae) pollens and pollens of birch, walnut, sheep sorrel, oak and willow, which are in the air around the same time as grass pollens, are important in clinical medicine, because of their high positive ratio. And in this research, each positive ratio is overlapping, so it is necessary to search an antigen hemology.
Assuntos
Antígenos/imunologia , Pólen/imunologia , Testes Cutâneos , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: 1) To estimate the effectiveness of intranasal administration of CpG DNA alone on allergic rhinitis compared with intradermal administration; and 2) to find out how CpG DNA therapy is useful in treatment of allergic rhinitis. STUDY DESIGN: Mice were intraperitoneally sensitized and intranasally challenged with Japanese cedar. Therapy with CpG DNA alone was also performed during challenge, either intranasally or intradermally. Immunologic variables and nasal symptom were studied. RESULTS: Intranasal administration of CpG DNA alone significantly reduced the levels of IgE, IL-5 productions from nasal lymphocytes and splenocytes, nasal eosinophilia, and nasal symptoms, although intradermal administration of CpG DNA alone showed no significant reduction. CONCLUSION: This study demonstrated that CpG DNA has effects not only on splenocytes but also on nasal lymphocytes to attenuate allergic rhinitis, and that intranasal administration, but not intradermal administration, of CpG DNA alone during allergen exposure is useful for control of allergic rhinitis.
Assuntos
Alérgenos/imunologia , Ilhas de CpG/imunologia , Cryptomeria/imunologia , Pólen/imunologia , Rinite/tratamento farmacológico , Administração Cutânea , Administração Intranasal , Administração Oral , Animais , Ensaio de Imunoadsorção Enzimática , Eosinofilia/prevenção & controle , Epitopos de Linfócito T , Feminino , Imunoglobulina E/imunologia , Interleucina-5/imunologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Rinite/imunologiaRESUMO
CONCLUSIONS: Allergic responses specific to the corresponding proteases were reduced by protease inhibitors, suggesting promise as potent treatments for allergic rhinitis and other allergic conditions. OBJECTIVE: Allergic diseases, such as allergic rhinitis, are caused by the overproduction of IgE antibodies to various allergens. Many reported allergens are proteases that are cysteine, serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64 inhibitor with cysteine protease allergens inhibits the IgE response to the same allergens. However, whether inhibitors of the other protease families reduce IgE levels and whether protease inhibitors reduce allergic symptoms remain controversial. Therefore, we compared the abilities of active and inhibitor-blocked inactive forms of proteases to generate IgE and allergic symptoms in this study to evaluate associations between the allergic response and protease inhibitors. MATERIALS AND METHODS: We measured levels of IgE, IgG1, IgG2a, and IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal rubbing behavior in mice immunized with active or inactive forms of bromelain, chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease, an aspartic protease and a metalloprotease, respectively). RESULTS: All the inhibitors reduced IgE and IgG1 production in response to corresponding enzymes, and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as sneezing and nasal rubbing.
Assuntos
Alérgenos/imunologia , Peptídeo Hidrolases/imunologia , Inibidores de Proteases/farmacologia , Rinite Alérgica Perene/tratamento farmacológico , Animais , Hipersensibilidade/tratamento farmacológico , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Inibidores de Proteases/uso terapêutico , Rinite Alérgica Perene/imunologiaRESUMO
Ascofuranone, an antibiotic isolated from Ascochyta visiae, showed trypanocidal activity in Trypanosoma vivax-infected mice. A single dose of 50 mg/kg ascofuranone effectively cured the mice without the help of glycerol. Repeated administrations of this drug further enhanced its chemotherapeutic effect. After two, three, and four consecutive days treatment, the doses needed to cure the infection decreased to 25, 12, and 6 mg/kg, so that the total doses administered were 50, 36 and 24 mg/kg, respectively. Ascofuranone (50 mg/kg) also had a prophylactic effect against T. vivax infection within the first two days after administration. This prophylactic activity diminished to 80% by day 3 and completely disappeared four days after administration. Of particular interest in this study was that ascofuranone had trypanocidal activity in T. vivax-infected mice in the absence of glycerol, whereas co-administration of glycerol or repeated administrations of this drug are needed for Trypanosoma brucei brucei infection. Our present results strongly suggest that ascofuranone is also an effective tool in chemotherapy against African trypanosomiasis in domestic animals.
Assuntos
Sesquiterpenos/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma vivax , Tripanossomíase Africana/tratamento farmacológico , Animais , Modelos Animais de Doenças , Glicerol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sesquiterpenos/administração & dosagem , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Resultado do Tratamento , Tripanossomicidas/administração & dosagem , Tripanossomicidas/farmacologia , Trypanosoma vivax/efeitos dos fármacos , Tripanossomíase Africana/parasitologiaRESUMO
The therapeutic effects of artesunate against experimental Schistosoma mansoni infection in mice were analyzed. Previous studies showed that artesunate is highly effective against S. japonicum infection, but the action of this drug against S. mansoni remained uncovered. The present study examines the optical conditions for artesunate against S. mansoni and evaluates the effects of inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni were orally administered with artesunate according to different schedules. Four consecutive administrations of 300 mg/kg of artesunate at 2-week intervals conferred almost total protection without the development of pathological lesions in the liver. The significant reduction in the number of eggs produced by surviving worms and the status of egg maturation suggested that artesunate inhibits sexual maturation. Electron microscopy revealed that artesunate caused morphological damage, especially on the worm tegument. Artesunate was also very effective in iron-deficient mice. Furthermore, the efficacy of artesunate was equal to or better than that of artemether against S. japonicum infection. Considering that artemether is more toxic, artesunate is currently one of the most efficient drugs against immature S. mansoni.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Anemia Ferropriva/complicações , Animais , Antimaláricos/farmacologia , Artemisininas/farmacologia , Artesunato , Feminino , Hepatomegalia/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Oviposição/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Schistosoma mansoni/ultraestrutura , Esquistossomose mansoni/complicações , Sesquiterpenos/farmacologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To study the prophylactic effect of artesunate against the infection of Schistosoma mansoni in mice and its optimal scheme for preventing schistosomiasis mansoni. METHODS: BALB/c mice were infected by tail dipping method with S. mansoni cercariae. Mice were administered orally with artesunate at different developmental stage of the parasite, with different regimens. The reduction rates of total and female worms, the number of eggs in the liver and intestine, and the fecundity were calculated and treated statistically. RESULTS: The optimal dosage of artesunate to prevent murine schistosomiasis was 300 mg/kg. The parasite was found to be especially susceptible to artesunate in its schistosomula stage of 14 and 21 d after infection, resulting in worm reduction rate of 84% and 93% respectively compared with control. High protection was reached with worm reduction rate of 99% by the regimens of 300 mg/kg once a week for 4 consecutive weeks beginning 14 d after infection. The fecundity was significantly suppressed, suggesting that the drug inhibited sexual maturation of female worms. The effective protection could also be gained with prolonged interval time of two weeks with worm reduction rate of 97% and 96% beginning 14 or 21 d after infection. CONCLUSION: Artesunate kills schistosomula and reduces the fecundity of females effectively, the infected mice do not develop schistosomiasis mansoni when treated with artesunate. It's proposed that an optimal scheme for field use be the first administration 14 or 21 days after infection with 1 or 2 weeks interval.