Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance L...Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 1C. For an isocratic run, the fiux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 mL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at 20 1C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.展开更多
The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration,aiming at reducing the frequency of administration and improvin...The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration,aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile.Chitosan microspheres were produced under fiuidized bed,followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm.The pellets were then coated with Kollidon VA64 and Kollicoat MAE100P in water dispersion to depict a sustained release profile.Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine.Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine.展开更多
AIM To identify significant liver disease [including nodular regenerative hyperplasia(NRH)] in asymptomatic Didanosine(DDI) exposed human immunodeficiency virus(HIV) positive patients.METHODS Patients without known li...AIM To identify significant liver disease [including nodular regenerative hyperplasia(NRH)] in asymptomatic Didanosine(DDI) exposed human immunodeficiency virus(HIV) positive patients.METHODS Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography(TE). Those with alanine transaminase(ALT) above upper limit normal and/or TE > 7.65 k Pa underwent ultrasound scan(U/S). Patients with:(1) abnormal U/S; or(2) elevated ALT plus TE > 7.65 k Pa;or(3) TE > 9.4 k Pa were offered trans-jugular liver biopsy(TJLB) with hepatic venous pressure gradient(HVPG) assessment.RESULTS Ninety-nine patients were recruited, median age 50 years(range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years(range 0.5-14.6). Eighty-one had a valid TE readings(interquartile range/score ratio < 0.3): 71(88%) < 7.65 k Pa, 6(7%) 7.65-9.4 k Pa and 4(6%) > 9.4 k Pa. Seventeen(17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mm Hg. Commonest histological findings were steatosis(n = 6), normal architecture(n = 4) and NRH(n = 2), giving a prevalence of previously undiagnosed NRH of 2%(95%CI: 0.55%, 7.0%).CONCLUSION A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.展开更多
By double beam and double wave interferomatric (DDI) method, the optical constants of thin films, i.e. refractive index, extinction coefficient and thickness may be determined in infrared (3.39 μm) and in visible (...By double beam and double wave interferomatric (DDI) method, the optical constants of thin films, i.e. refractive index, extinction coefficient and thickness may be determined in infrared (3.39 μm) and in visible (0.633 μm) wavelengths in the same optical path with a tunable double wave He Ne laser designed by ourselves. The measuring principle and the device are describod.展开更多
采用傅里叶变换红外(FT-IR)光谱法研究了二聚脂肪酸二异氰酸酯(DDI)/端羟基聚丁二烯(HTPB)体系的固化反应动力学,并与异佛尔酮二异氰酸酯(IPDI)/HTPB体系进行了比较。初步探索了DDI在HTPB推进剂中的应用。结果表明,DDI/HTPB体系的固化...采用傅里叶变换红外(FT-IR)光谱法研究了二聚脂肪酸二异氰酸酯(DDI)/端羟基聚丁二烯(HTPB)体系的固化反应动力学,并与异佛尔酮二异氰酸酯(IPDI)/HTPB体系进行了比较。初步探索了DDI在HTPB推进剂中的应用。结果表明,DDI/HTPB体系的固化反应为二级反应,表观活化能为37.02 k J·mol-1,相比IPDI/HTPB体系降低了3.5 k J·mol-1,说明DDI的反应活性稍高于IPDI,反应活性适中,可作为低毒固化剂应用于HTPB推进剂中。DDI/HTPB体系推进剂具有较好的常温力学性能,抗拉强度为0.85 MPa时,最大伸长率为44.1%,可基本满足推进剂的常温力学性能要求。展开更多
基金supported by the Research Foundation of the State of So Paulo (FAPESP/Brazil)National Council of Technological and Scientific Development (CNPq/Brazil)
文摘Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 1C. For an isocratic run, the fiux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 mL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at 20 1C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.
基金the financial support from the Fundao de Amparo a Pesquisa do Estado de So Paulo(FAPESP/Brazil)the Conselho Nacional de Pesquisa(CNPq,Brazil)
文摘The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration,aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile.Chitosan microspheres were produced under fiuidized bed,followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm.The pellets were then coated with Kollidon VA64 and Kollicoat MAE100P in water dispersion to depict a sustained release profile.Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine.Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine.
基金Supported by The British HIV Association Research Award 2009-￡7800 in total awarded
文摘AIM To identify significant liver disease [including nodular regenerative hyperplasia(NRH)] in asymptomatic Didanosine(DDI) exposed human immunodeficiency virus(HIV) positive patients.METHODS Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography(TE). Those with alanine transaminase(ALT) above upper limit normal and/or TE > 7.65 k Pa underwent ultrasound scan(U/S). Patients with:(1) abnormal U/S; or(2) elevated ALT plus TE > 7.65 k Pa;or(3) TE > 9.4 k Pa were offered trans-jugular liver biopsy(TJLB) with hepatic venous pressure gradient(HVPG) assessment.RESULTS Ninety-nine patients were recruited, median age 50 years(range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years(range 0.5-14.6). Eighty-one had a valid TE readings(interquartile range/score ratio < 0.3): 71(88%) < 7.65 k Pa, 6(7%) 7.65-9.4 k Pa and 4(6%) > 9.4 k Pa. Seventeen(17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mm Hg. Commonest histological findings were steatosis(n = 6), normal architecture(n = 4) and NRH(n = 2), giving a prevalence of previously undiagnosed NRH of 2%(95%CI: 0.55%, 7.0%).CONCLUSION A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.
文摘By double beam and double wave interferomatric (DDI) method, the optical constants of thin films, i.e. refractive index, extinction coefficient and thickness may be determined in infrared (3.39 μm) and in visible (0.633 μm) wavelengths in the same optical path with a tunable double wave He Ne laser designed by ourselves. The measuring principle and the device are describod.
文摘供者来源性感染（donor derived infection,DDI）是指在器官捐献后,捐献者体内存在的病原体通过器官移植过程使受者罹患相同的感染。产生DDI的客观原因是绝大部分捐献者在原发疾病救治过程中可能经历重大手术、持续气管插管或切开行机械通气,留置深静脉导管、导尿管等各种导管,时常需要血液透析、人工肝、体外膜肺氧合等治疗,都曾入住重症监护病房（intensive care unit,ICU）,
文摘采用傅里叶变换红外(FT-IR)光谱法研究了二聚脂肪酸二异氰酸酯(DDI)/端羟基聚丁二烯(HTPB)体系的固化反应动力学,并与异佛尔酮二异氰酸酯(IPDI)/HTPB体系进行了比较。初步探索了DDI在HTPB推进剂中的应用。结果表明,DDI/HTPB体系的固化反应为二级反应,表观活化能为37.02 k J·mol-1,相比IPDI/HTPB体系降低了3.5 k J·mol-1,说明DDI的反应活性稍高于IPDI,反应活性适中,可作为低毒固化剂应用于HTPB推进剂中。DDI/HTPB体系推进剂具有较好的常温力学性能,抗拉强度为0.85 MPa时,最大伸长率为44.1%,可基本满足推进剂的常温力学性能要求。
