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OBJECTIVE: To understand the dynamic status of schistosomiasis epidemic situation and Oncomelania hupensis snail status before and after the schistosomiasis transmission interrupted in the mountainous areas of Yunnan Province. METHODS: The data of schistosomiasis epidemic situation and snail status were collected and analyzed statistically in Jianchuan County from 10 years before the schistosomiasis transmission interrupted to 2008. RESULTS: The schistosomiasis control began in Jianchuan County from 1954. In 1976, the criteria of schistosomiasis endemic controlled were reached, and the infection rate of population was 0.65% and the infection rate of snails was 0.40%. In 1981, the criteria of schistosomiasis transmission controlled were reached, and the infection rate of population was 0.34% and the infection rate of snails was 1.41%. In 1993, the criteria of schistosomiasis transmission interrupted were reached, and the infection rate of population was 0 and the infection rate of snails was 0. There was a fluctuation in the schistosomiasis epidemic situation and snail status during the whole control duration, but the trend was decreasing. CONCLUSION: The time from schistosomiasis endemic controlled to transmission controlled is relatively short, but the time from transmission controlled to transmission interrupted is relatively long. In the original schistosomiasis endemic areas, there might be some areas where there is no the disease bud there still are snails.
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Enfermedades de los Bovinos/epidemiología , Esquistosomiasis/epidemiología , Esquistosomiasis/veterinaria , Adolescente , Adulto , Anciano , Animales , Bovinos , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/prevención & control , China/epidemiología , Reservorios de Enfermedades/parasitología , Enfermedades Endémicas/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Schistosoma/fisiología , Esquistosomiasis/parasitología , Esquistosomiasis/prevención & control , Caracoles/crecimiento & desarrollo , Caracoles/parasitología , Adulto JovenRESUMEN
The sulfamide moiety has been utilized to design novel HDAC inhibitors. The potency and selectivity of these inhibitors were influenced both by the nature of the scaffold, and the capping group. Linear long-chain-based analogs were primarily HDAC6-selective, while analogs based on the lysine scaffold resulted in potent HDAC1 and HDAC6 inhibitors.
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Amidas/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores de Histona DesacetilasasRESUMEN
Nonselective inhibitors of human histone deacetylases (HDAC) are known to have antitumor activity in mice in vivo, and several of them are under clinical investigation. The first of these, Vorinostat (SAHA), has been approved for treatment of cutaneous T-cell lymphoma. Questions remain concerning which HDAC isotype(s) are the best to target for anticancer activity and whether increased efficacy and safety will result with an isotype-selective HDAC inhibitor. We have developed an isotype-selective HDAC inhibitor, MGCD0103, which potently targets human HDAC1 but also has inhibitory activity against HDAC2, HDAC3, and HDAC11 in vitro. In intact cells, MGCD0103 inhibited only a fraction of the total HDAC activity and showed long-lasting inhibitory activity even upon drug removal. MGCD0103 induced hyperacetylation of histones, selectively induced apoptosis, and caused cell cycle blockade in various human cancer cell lines in a dose-dependent manner. MGCD0103 exhibited potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDAC inhibitory activity was required for these effects. In vivo, MGCD0103 significantly inhibited growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. Our findings suggest that the isotype-selective HDAC inhibition by MGCD0103 is sufficient for antitumor activity in vivo and that further clinical investigation is warranted.
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Apoptosis/efectos de los fármacos , Benzamidas/farmacología , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores de Histona Desacetilasas , Neoplasias Pulmonares/tratamiento farmacológico , Pirimidinas/farmacología , Acetilación , Animales , Benzamidas/farmacocinética , Inhibidores Enzimáticos/farmacocinética , Femenino , Histona Desacetilasa 1 , Histona Desacetilasa 2 , Histona Desacetilasas/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Técnicas In Vitro , Isoenzimas , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Pirimidinas/farmacocinética , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/metabolismo , Células Tumorales Cultivadas , Vorinostat , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
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Antineoplásicos/síntesis química , Benzamidas/síntesis química , Inhibidores de Histona Desacetilasas , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , Antineoplásicos/química , Benzamidas/química , Benzamidas/farmacología , Dominio Catalítico , Línea Celular , Histona Desacetilasa 1 , Histona Desacetilasas/química , Histona Desacetilasas/metabolismo , Humanos , Modelos Moleculares , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/metabolismo , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To study the therapeutic effect of traditional Chinese herbal medicinal preparation Tangshenqing (TSQ) combined with alprostadil in the treatment of early- and intermediate-stage diabetic nephropathy (DN). METHODS: One hundred and twenty DN patients were randomized into 3 groups for different treatment protocols. The patients in the control group were given the basic treatment (low-protein diabetic diet and rigorous control of blood glucose, blood pressure, and blood fatty acid), and those in treatment group A received TSQ (containing Astragalus membranaceus, Panax notoginseng, Epimedium brevicornum, etc) in addition to the basic treatment, and those in treatment group B were treated with alprostadil injections (for 14 consecutive days) in addition to the treatment given in group A. Therapeutic effect evaluation was carried out after a 30-day treatment in all the patients. RESULTS: The overall efficaey rate of the treatment was 78.37% in the control group, 88.57% in the treatment group A, and 94.44% in treatment group B, suggesting better therapeutic effect in the latter two groups than in the control group (P<0.05). Patients in all the 3 groups exhibited symptomatic improvement of various degrees, but the treatment group B had the best results. After the treatments, the patients' blood glucose and fatty acids were lowered, without obvious difference between the 3 groups. Compared with the control group, the patients in the two treatment groups showed significant reduction in fibrinogen, 24-h urine microprotein and urine protein after the treatment (P<0.01 or 0.05). CONCLUSION: Combined use of traditional Chinese herbal medicine TSQ and alprostadil injections produces definite therapeutic effect on early- to intermediate-stage DN.
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Nefropatías Diabéticas/terapia , Medicina Integrativa/métodos , Medicina Tradicional China/métodos , Anciano , Albuminuria/metabolismo , Glucemia/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología , Femenino , Fibrinógeno/metabolismo , Humanos , Riñón/efectos de los fármacos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
In the title compound, C(8)H(11)BrN(+)·Br(-)·H(2)O, a network of N-Hâ¯O, N-Hâ¯Br and O-Hâ¯Br hydrogen bonds helps to consolidate the crystal packing.
RESUMEN
OBJECTIVES: To evaluate the efficacy of intrameatal application of low dosage alprostadil (PGE1) cream (300 mcg) for the treatment of erectile dysfunction (ED). METHODS: A total of 43 ED patients were selected in the study based on the inclusion criteria. All of the patients signed informed consent forms and entered a 4-week open-label clinical study. A dosage of 300 mg PGE1 in 75 mg cream was applied intrameatally. RESULTS: The results showed that the primary efficacy (IIEF Q3 + Q4) reached 70.73% after application of the cream. The successful intercourse rate was 86.41%. Based on the GAQ (global assessment Question); 73.17% of the patients were satisfied with their sexual life. At the same time, all of the secondary criteria supported the primary efficacy results. Two patients withdrew during the study period. Six patients (14.63%) had urethral pain or penile redness, which were mostly mild and transient. CONCLUSIONS: With intrameatal low dosage (300 mcg PGE1) of the PGE1 cream can achieve an equivalent efficacy as that with the full dosage.