Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 123
Article in Chinese | WPRIM | ID: wpr-828543


OBJECTIVE@#To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use.@*METHODS@#Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r).@*RESULTS@#The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results.@*CONCLUSIONS@#In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.

Databases, Pharmaceutical , Decision Making, Computer-Assisted , Drug Monitoring , Drug-Related Side Effects and Adverse Reactions , HIV Protease Inhibitors , Pharmacology , Humans , Liver , Lopinavir , Toxicity , Models, Statistical , Reproducibility of Results , Software , Reference Standards
Rev. chil. infectol ; 36(4): 490-495, ago. 2019. tab
Article in Spanish | LILACS | ID: biblio-1042666


Resumen Introducción: El impacto del cambio de terapia antiretroviral (TAR) para tratar la dislipidemia en pacientes infectados por VIH no ha sido reportado en Chile. Objetivo: Evaluar la efectividad y seguridad a 12 meses del cambio de TAR a esquema con raltegravir (RAL) para tratar la dislipidemia. Material y Métodos: Cohorte retrospectiva de pacientes con infección por VIH en TAR, atendidos en Fundación Arriarán, con dislipidemia y que cambiaron a esquema con RAL para tratarla. Resultados: Se incluyó 73 casos, en TAR con inhibidores no nucleosídicos de transcriptasa reversa (INNTR; 50,7%) o inhibidores de proteasa (IP; 49,3%), con dislipidemia mixta (42,5%) o hipertrigliceridemia aislada (57,5%). La mediana de colesterol total (CT) y triglicéridos (TG) basales era 228 mg/dl y 420 mg/dl, respectivamente. El 94,5% tenía carga viral (CV) indetectable. Se modificó TAR de base en 58,4%; 89,1% recibía hipolipemiantes. Las concentraciones plasmáticas de lípidos descendieron significativamente a 12 meses (TG= −43,6%; CT= −19,3%). Ningún paciente presentó fracaso virológico, aunque 10,9% tuvo viremia detectable a 12 meses, mayoritariamente transitoria. Conclusiones: El cambio de TAR a RAL en pacientes dislipidémicos tratados con INNTR o IP reduce significativamente las concentraciones plasmáticas de TG y CT a 12 meses. Es una estrategia segura, pero puede observarse viremia transitoria.

Background: The impact of switching antiretroviral therapy (ART) regimen for dyslipidemia management in HIV-infected (HIV+) patients has not been reported in Chile. Aim: To assess effectiveness and safety at 12 months after switching to raltegravir-based regimen for dyslipidemia management. Methods: Retrospective cohort of HIV+ patients receiving ART at Arriaran Foundation, with dyslipidemia switched to raltegravir-based regimen for lipid management. Results: 73 patients were included, receiving ART based in nonnucleoside reverse transcriptase inhibitor (NNRTI; 50,7%) or protease inhibitor (PI; 49,3%), with mixed dyslipidemia (42,5%) or isolated hypertriglyceridemia (57,5%). At baseline, median total cholesterol (TC) and triglycerides (TG) were 228 mg/dl and 420 mg/dl, respectively; undetectable viral load (VL) was present in 94,5% of patients. Backbone ART was switched in 58,4% and lipid-lowering therapy was used by 89,1% of them. At 12 months, there was a significant decrease in TG (-43,6%) and TC (-19,3%). No cases of virologic failure were observed, although 10,9% of patients had detectable VL at 12 months, mostly transient. Conclusions: Switching ART to raltegravir-based regimen in dyslipidemic patients receiving NNRTI or PI is associated with a significative decrease in TG and TC at 12 months. This strategy is safe, but VL can be increased temporarily.

Humans , Male , Female , Adult , Middle Aged , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , Dyslipidemias/prevention & control , Raltegravir Potassium/administration & dosage , HIV Infections/blood , Retrospective Studies , Cohort Studies , Follow-Up Studies , CD4 Lymphocyte Count , Viral Load
Braz. j. infect. dis ; 21(4): 396-401, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-888887


Abstract Introduction: The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Methods: Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Results: Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. Conclusions: The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are needed to inform the predictors of transmitted resistance and the antiretroviral therapy outcomes among these population.

Humans , Male , Female , Adult , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , HIV Protease Inhibitors/therapeutic use , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Brazil , HIV Infections/genetics , HIV Infections/drug therapy , Acute Disease , Genotype , Mutation
Rev. méd. Chile ; 144(7): 931-936, jul. 2016. ilus, tab
Article in Spanish | LILACS | ID: lil-794007


We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months.

Humans , Male , Adult , Bronchodilator Agents/adverse effects , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Cushing Syndrome/chemically induced , Salmeterol Xinafoate/adverse effects , Fluticasone/adverse effects , Nebulizers and Vaporizers , Bronchodilator Agents/therapeutic use , HIV Protease Inhibitors/therapeutic use , Cushing Syndrome/diagnosis , Drug Interactions , Salmeterol Xinafoate/therapeutic use , Fluticasone/therapeutic use
Braz. j. infect. dis ; 20(2): 155-159, Mar.-Apr. 2016. tab
Article in English | LILACS | ID: lil-780810


Abstract Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1 μg mL−1 for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 μg mL−1and from 0.0625 to 1 μg mL−1 for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 μg mL−1 and from 0.0039 to 0.0312 μg mL−1 for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p < 0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum.

HIV Protease Inhibitors/pharmacology , Itraconazole/pharmacology , Ritonavir/pharmacology , Saquinavir/pharmacology , Histoplasma/drug effects , Antifungal Agents/pharmacology , Microbial Sensitivity Tests , Drug Synergism
Braz. j. infect. dis ; 20(1): 14-18, Jan.-Feb. 2016. tab, graf
Article in English | LILACS | ID: lil-776466


Abstract In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048), SAH (F = 6.964; p = 0.009), and age over 50 years (F = 45.81; p < 0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05) and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.

Adult , Female , Humans , Male , Middle Aged , Young Adult , Anti-HIV Agents/adverse effects , Kidney/drug effects , Tenofovir/adverse effects , Anti-HIV Agents/administration & dosage , Drug Therapy, Combination/adverse effects , Follow-Up Studies , Glomerular Filtration Rate/drug effects , HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , Kidney/physiopathology , Retrospective Studies , Risk Factors , Time Factors , Tenofovir/administration & dosage
Rev. chil. pediatr ; 86(4): 236-243, ago. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-764079


Introducción: La respuesta inmune a los antígenos de las vacunas está disminuida en los niños con cáncer. El objetivo de este estudio fue evaluar la seroconversión frente a vacuna ADN recombinante contra hepatitis B al momento del inicio de la quimioterapia y/o remisión en niños con cáncer. Pacientes y método: Estudio prospectivo, bicéntrico, controlado, no aleatorizado de niños con diagnóstico reciente de cáncer pareados con niños sanos. Los casos fueron vacunados a tiempo 0, 1 y 6 meses, a dosis de 20 y 40 μg si eran < ó > 10 años, respectivamente, con vacuna ADN recombinante contra hepatitis B, en el momento del diagnóstico en el caso de los tumores sólidos y luego de la remisión en el caso de los tumores hematológicos. El grupo control recibió el mismo esquema, con dosis de 10 o 20 μg respectivamente. Se midieron anticuerpos séricos anti-HBs a los 2, 8 y 12 meses posvacunación. Seroconversión se definió como títulos anti-HBs > 10 mUI/ml al octavo mes. Resultados: Un total de 78 niños con cáncer y 25 controles fueron evaluados con títulos anti-HBs al octavo mes. La tasa de seroconversión fue de 26,9%, en niños con cáncer, sin diferencia por edad, género ni tipo de tumor (p = 0,13; 0,29; y 0,44, respectivamente), y de 100% en el grupo control (p < 0,0001, comparado con los niños con cáncer). En el seguimiento a los 12 meses solo el 31,9% de los niños con cáncer presentaba títulos anti-HBs > 10 mUI/ml. Conclusiones: La vacunación contra hepatitis B con vacuna ADN recombinante, con esquema reforzado de 3 dosis, en el momento del inicio de la quimioterapia y/o remisión provee una respuesta inmune insuficiente en la mayoría de los niños con cáncer. En esta población debieran evaluarse vacunas de tercera generación, con adyuvantes más inmunogénicos, esquemas reforzados a los 0, 1, 2 y 6 meses, medición de títulos de anticuerpos al octavo y duodécimo mes, eventual uso de refuerzos y reevaluación de inmunogenicidad si correspondiese.

Introduction: Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. Patients and method: Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. Results: A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml. Conclusions: Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12 h to evaluate the need for further booster doses.

Humans , HIV , Anti-HIV Agents/immunology , Anti-HIV Agents/pharmacology , /immunology , HIV Infections/drug therapy , Liposomes/immunology , Liposomes/pharmacology , HIV , Antiretroviral Therapy, Highly Active/methods , Drug Carriers/chemistry , HIV Infections/immunology , HIV Protease Inhibitors/immunology , HIV Protease Inhibitors/pharmacology , Jurkat Cells , Lipids/chemistry , Lipids/immunology , Nanoparticles/chemistry , Nevirapine/immunology , Nevirapine/pharmacology , Saquinavir/immunology , Saquinavir/pharmacology
Rev. med. Rosario ; 81(1): 19-23, ene.-abr. 2015. tab
Article in Spanish | LILACS | ID: lil-758454


Objetivo. Describir la función sexual de un grupo de mujeres con VIH bajo tratamiento antirretroviral. Evaluar si existe diferencia entre las tratadas con un esquema que contiene Inhibidores No Nucleósidos de la Transcriptasa Inversa (INNTI) y aquéllas que reciben Inhibidores de la Proteasa (IP). Material y métodos. Estudio descriptivo, transversal. Muestra: 92 pacientes mujeres con VIH bajo tratamiento antirretroviral, que son asistidas en el Instituto Centralizado de Asistencia e Investigación Clínica Integral (CAICI). Instrumento: Se les realizó una encuesta que consta de características demográficas, preguntas referidas al VIH y al The Female Sexual Function Index (FSFI). Análisis estadístico: se utilizó ANOVA, Kruskall-Wallis, Chi cuadrado, regresión logística y alpha de Cronbach. Resultados. Edad media: 42±10 años; 65% tenían pareja estable, siendo el 73% de estas sero-discordantes. La mayoría (45,7%) estaban en tratamiento antirretroviral por más de dos años, con una media de CD4 mayor a 500 cél/ml y el 90% con carga viral plasmática indetectable. El 64,1% presentaba otra enfermedad asociada, por lo que el 55,4% tomaba medicación concomitante. El 27,2% continuó con su actividad sexual luego del diagnóstico de VIH, pero el 26,1% nunca la retomó. La puntuación total alcanzada por medio del FSFI fue de 20,4±10,1 para las tratadas con IP y 20±10,6 para las tratadas con INNTI (p <0,005). Conclusiones. La muestra analizada presentó un puntaje compatible con disfunción sexual. No hubo diferencia estadísticamente significativa en la función sexual de las mujeres tratadas con IP y las tratadas con INNTI

Summary Objective: To describe the sexual function in a group of women with HIV on antiretroviral treatment. To assess whether there is a difference between those treated with Non-nucleoside Inhibitors of he Reverse Transcriptase (NNRTI) and those receiving protease inhibitors (PIs). Material and methods: Descriptive, transversal study. Study sample: 92 women with HIV on antiretroviral therapy who are assisted in the Central Institute of Integral Assistance and Clinical Research (CAICI). Instrument: They completed a survey consisting of questions about demographic characteristics, HIV, and The Female Sexual Function Index (FSFI). Statistical analysis: ANOVA, Kruskal-Wallis, Chi-square, logistic regression and Cronbach’s alpha. Results: Average age was 42±10 years; 65% had a steady partner, of which 73% were sero-discordant. Most patients (45.7%) had been on antiretroviral treatment for more than two years, with a mean CD4 greater than 500 cells/ml and 90% with undetectable plasma viral load. Other illnesses were present in 64.1%, and 55.4% were taking concomitant medication. Sexual activity after HIV diagnosis was continued by 27.2%, while 26.1% never resumed it. The total score achieved by the FSFI was 20.4±10.1 among those treated with IP and 20.0±10.6 among those treated with NNRTI(p<0.005). Conclusions: The score in the present sample supports the existence of sexual dysfunction. There was no statistically significant difference in the sexual function of women treated with either PI or NNRTI

Humans , Female , HIV , Sexuality , Treatment Outcome , Autoimmune Diseases/prevention & control , HIV Protease Inhibitors , Reverse Transcriptase Inhibitors/therapeutic use , HIV Reverse Transcriptase/therapeutic use
Article in Chinese | WPRIM | ID: wpr-246102


Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5'-methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4-Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N-[2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4-hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11). Among them, compounds 1 and 2 were new natural products. In the preliminary assays, none of the compounds exhibited obvious inhibition of HIV-1 protease activity (IC50 > 10 micromol x L(-1)).

Culture Media , Chemistry , Metabolism , HIV Protease , HIV Protease Inhibitors , Chemistry , Molecular Structure , Spectrometry, Mass, Electrospray Ionization , Streptomyces , Chemistry , Metabolism
Actual. SIDA. infectol ; 22(85): 47-52, set.2014. ilus
Article in Spanish | LILACS | ID: lil-780404


Dolutegravir (DTG) es un inhibidor de la integrasa del VIH aprobado recientemente como tratamiento por la FDA (Food and Drug Administration) en los Estados Unidos. Utilizado como parte de un tratamiento de primera línea, DTG es el único tratamiento antirretroviral frente al cual no se ha seleccionado resistencia en la clínica. Nuestra teoría es que esto se debe al prolongado tiempo de unión del DTG a la enzima integrasa así como a una capacidad de replicación muy disminuida por parte de los virus que podrían volverse resistentes al DTG. Además, conjeturamos que DTG podría ser utilizado en estrategias que apunten a la erradicación del VIH...

Dolutegravir (DTG) is an HIV integrase inhibitor that was recently approved for therapy by the Food and Drug Administration in the United States. When used as part of First-line therapy, DTG is the only HIV drug that has not selected for resistance mutations in the clinic. We believe that this is due to the long binding time of DTG to the integrase enzyme as well as greatly diminished replication capacity on the parte of viruses that might become resistant to DTG. We further speculatethat DTG might be able to be used in strategies aimed at HIV eradication...

Humans , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , HIV Protease Inhibitors/pharmacology , HIV Integrase/therapeutic use , Mutation
Mem. Inst. Oswaldo Cruz ; 109(4): 484-487, 03/07/2014. tab, graf
Article in English | LILACS | ID: lil-716314


Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

Animals , Cricetinae , Dietary Fats/blood , HIV Protease Inhibitors/pharmacology , Indinavir/pharmacology , Autoantibodies/blood , Biomarkers/blood , Blood Glucose/analysis , Cholesterol/blood , Heart/drug effects , Kidney/drug effects , Lipoproteins, LDL/drug effects , Models, Animal , Triglycerides/blood
Chinese Journal of Oncology ; (12): 324-328, 2014.
Article in Chinese | WPRIM | ID: wpr-328943


<p><b>OBJECTIVE</b>The study intended to investigate the effect and mechanism of endoplasmic reticulum stress on cisplatin resistance in ovarian carcinoma.</p><p><b>METHODS</b>RT-PCR and Western blot were used to test the expression of mTOR and Beclin1 mRNA and protein in ovarian cancer SKOV3 cells after saquinavir induction. MTT assay was used to analyze the influence of saquinavir on cisplatin sensitivity in SKOV3 cells.</p><p><b>RESULTS</b>The IC50 of SKOV3 cells was (5.490 ± 1.148) µg/ml. After induced by Saquinavair 10 µmol/L and 20 µmol/L, the IC50 of SKOV3 cells was increased to (11.199 ± 0.984) µg/ml and (14.906 ± 2.015) µg/ml, respectively. It suggested that the sensitivity of ovarian cancer cells to cisplatin was decreased significantly (P = 0.001). The expression of mTOR and Beclin1 mRNA and protein was significantly different among the five groups: the (Saquinavair+DDP) group of, Saquinavair group, LY294002 group, DDP group and control group (P < 0.001) . The expressions of mTOR and Beclin1 mRNA were highest in the (Saquinavair+DDP) group, 0.684 ± 0.072 and 0.647 ± 0.047, respectively; Secondly, the Saquinavair group, 0.577 ± 0.016 and 0.565 ± 0.037, respectively. The expressions of mTOR and Beclin1 proteins were also highest in the (Saquinavair+DDP) group, 0.624 ± 0.058 and 0.924 ± 0.033, respectively, followed by the Saquinavair group, 0.544 ± 0.019 and 0.712 ± 0.024. 3-MA inhibited the autophagy and restored cisplatin sensitivity in the SKOV3 cells after Saquinavir induced ER stress (P < 0.001).</p><p><b>CONCLUSIONS</b>Saquinavir can effectively induce endoplasmic reticulum stress in SKOV3 cells. Endoplasmic reticulum stress can decrease the sensitivity to cisplatin in SKOV3 cells. The mechanism of the decrease of sensitivity to cisplatin in SKOV3 cells may be that ERS regulates cell autophagy through the mTOR and Beclin1 pathways. ERS of tumor cells and autophagy may become a new target to improve the therapeutic effect of chemotherapy and to reverse the drug resistance in tumor treatment.</p>

Antineoplastic Agents , Pharmacology , Apoptosis Regulatory Proteins , Genetics , Metabolism , Autophagy , Beclin-1 , Cell Line, Tumor , Cisplatin , Pharmacology , Cystadenocarcinoma, Serous , Metabolism , Pathology , Drug Resistance, Neoplasm , Endoplasmic Reticulum Stress , Female , HIV Protease Inhibitors , Pharmacology , Humans , Membrane Proteins , Genetics , Metabolism , Ovarian Neoplasms , Metabolism , Pathology , RNA, Messenger , Saquinavir , Pharmacology , TOR Serine-Threonine Kinases , Genetics , Metabolism
Medicina (B.Aires) ; 73(4): 346-348, jul.-ago. 2013.
Article in Spanish | LILACS | ID: lil-694794


El ergotismo es una complicación de la intoxicación aguda y/o el abuso crónico de los derivados del ergot. Se manifiesta por síndrome vasomotor con enfermedad vascular periférica que frecuentemente compromete extremidades. Presentamos cuatro casos de pacientes infectados con el virus de la inmunodeficiencia humana 1 (HIV-1), en tratamiento con antirretrovirales que incluyen inhibidores de la proteasa reforzados con ritonavir, y que habían recibido ergotamina como automedicación. Ellos desarrollaron síntomas de enfermedad vascular periférica y al examen físico sus pulsos estaban disminuidos o ausentes. El Doppler arterial confirmó signos de espasmo arterial difuso en dos de ellos. Se hizo diagnóstico de ergotismo secundario a la asociación de ergotamina-inhibidores de la proteasa. Los pacientes fueron tratados con la discontinuación de las drogas involucradas (inhibidores de la proteasa y ergotamina), bloqueantes cálcicos, profilaxis antitrombótica con enoxaparina, antiagregación con ácido acetil salicílico y uno ellos recibió pentoxifilina e infusión de prostaglandinas vasodilatadoras con mejoría de los síntomas. Discutimos la presentación clínica de esta interacción medicamentosa, difícil de diagnosticar correctamente sin una fuerte sospecha de su existencia.

Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.

Adult , Female , Humans , Male , Middle Aged , Adrenergic alpha-1 Receptor Agonists/adverse effects , Ergotamine/adverse effects , Ergotism/etiology , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Ritonavir/adverse effects , Drug Interactions , Drug Therapy, Combination/adverse effects
Article in Portuguese | LILACS | ID: lil-677940


O darunavir é um inibidor de protease utilizado para o tratamento da infecção pelo HIV. Trata-se de um dos pilares da terapia de coquetel para pacientes portadores do vírus. O controle de qualidade na indústria farmacêutica, para identificação do teor de substância ativa e estudo das características físico-químicas do fármaco, é de fundamental importância para garantir a qualidade do produto final. O darunavir, até então, não possui métodos de análise padronizados em compêndios oficiais. Este fato justifica novas pesquisas nesta área para o desenvolvimento e validação de métodos analíticos, bem como a análise químico-farmacêutica para este fármaco tanto na matéria-prima como no produto acabado. Dessa forma, neste trabalho foram realizados (a) peso médio; (b) determinação do ponto de fusão; (c) cromatografia em camada delgada; (d) análise na região do ultravioleta; (e) análise na região do infravermelho e (f) cromatografia líquida de alta eficiência. Através do desenvolvimento das técnicas propostas é possível avaliar qualitativamente a qualidade de darunavir em comprimidos.

Darunavir is a protease inhibitor used in the treatment of HIV infection. It is a pillar of the drug cocktail for patients diagnosed with the virus. Quality control in the pharmaceutical industry, to verify the content of active substance and study the physicochemical characteristics of the drug, is essential to ensure final product quality. Until now, standardized methods for the analysis of darunavir have not been available in official compendia. This justifies new research, to develop and validate analytical methods, as well as physicochemical and pharmaceutical analysis for this drug, both as a raw material and a finished product. Thus, in this study, (a) the average weight of darunavir tablets and (b) the melting point of the pure drug were determined, and the following analytical techniques were performed: (c) thin-layer chromatography, (d) ultraviolet spectroscopy, (e) infrared spectroscopy and (f) high performance liquid chromatography. By developing the above techniques, it is possible to make a qualitative assessment of the quality of darunavir tablets.

Tablets/analysis , HIV Protease Inhibitors , Evaluation Studies as Topic
Rev. Inst. Med. Trop. Säo Paulo ; 55(1): 65-67, Jan.-Feb. 2013. tab
Article in English | LILACS | ID: lil-661105


The introduction of highly active antiretroviral therapy (HAART) has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE). These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API) on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

La introducción de la terapia antirretroviral de alta efectividad ha causada una marcada reducción en la ocurrencia y curso clínico de las infecciones parasitarias, incluyendo la toxoplasmosis encefálica (TE). Estos cambios han sido atribuidos a la restauración celular. Este estudio fue desarrollado para examinar la actividad de seis inhibidores de proteasas antirretrovirales (IPA) sobre taquizoitos de Toxoplasma gondii. Los seis IPA mostraron actividad anti-Toxoplasma, con valores de CI50 entre 1.4 y 6.6 µg/mL. Futuros estudios a nivel molecular deben ser realizados, los cuales podrán delucidar si el uso de IPA pudiera beneficiar o no a los pacientes que sufren de TE.

Animals , Female , Mice , HIV Protease Inhibitors/pharmacology , Toxoplasma/drug effects , Parasitic Sensitivity Tests
West Indian med. j ; 61(9): 932-936, Dec. 2012. ilus
Article in English | LILACS | ID: lil-694370


The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Adult , Humans , Male , Carbamates/adverse effects , Cardiomyopathies/drug therapy , Creatine Kinase/blood , Cyclohexanes/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Fatty Liver/chemically induced , HIV Fusion Inhibitors/adverse effects , HIV Infections/drug therapy , HIV Integrase Inhibitors/adverse effects , HIV Protease Inhibitors/adverse effects , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/chemically induced , Organophosphates/adverse effects , Pyrrolidinones/adverse effects , Sulfonamides/adverse effects , Triazoles/adverse effects , Carbamates/therapeutic use , Cyclohexanes/therapeutic use , Drug Substitution , Drug Therapy, Combination , Fatty Liver/diagnosis , HIV Fusion Inhibitors/therapeutic use , HIV Integrase Inhibitors/therapeutic use , HIV Protease Inhibitors/therapeutic use , Liver Cirrhosis/diagnosis , Organophosphates/therapeutic use , Pyrrolidinones/therapeutic use , Sulfonamides/therapeutic use , Triazoles/therapeutic use