RESUMO
BACKGROUND: Functional assessment of the future liver remnant (FLR) after major hepatectomy is essential but often difficult in patients with biliary malignancy, owing to obstructive jaundice and portal vein embolization. This study evaluated whether a novel index using gadoxetate disodium-enhanced MRI (EOB-MRI) could predict posthepatectomy liver failure (PHLF) after major hepatectomy for biliary malignancy. METHODS: The remnant hepatocellular uptake index (rHUI) was calculated in patients undergoing EOB-MRI before major hepatectomy for biliary malignancy. Receiver operating characteristic (ROC) curve analyses were used to evaluate the accuracy of rHUI for predicting PHLF grade B or C, according to International Study Group of Liver Surgery criteria. Multivariable logistic regression analyses comprised stepwise selection of parameters, including rHUI and other conventional indices. RESULTS: This study included 67 patients. The rHUI accurately predicted PHLF (area under the curve (AUC) 0.896). A cut-off value for rHUI of less than 0.410 predicted all patients who developed grade B or C PHLF. In multivariable analysis, only rHUI was an independent risk factor for grade B or C PHLF (odds ratio 2.0 × 103, 95 per cent c.i. 19.6 to 3.8 × 107; P < 0.001). In patients who underwent preoperative portal vein embolization, rHUI accurately predicted PHLF (AUC 0.885), whereas other conventional indices, such as the plasma disappearance rate of indocyanine green of the FLR and FLR volume, did not. CONCLUSION: The rHUI is potentially a useful predictor of PHLF after major hepatectomy for biliary malignancy.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Gadolínio DTPA , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
Atmospheric CO2 concentrations increased significantly over the last century and continuing increases are expected to have significant effects on current ecosystems. This study evaluated the behavioural and physiological (hormone status, muscle structure) effects of prolonged CO2 exposure in young female Wistar rats exposed at 700ppm of CO2 during 6h a day for 15days. Prolonged CO2 exposure, though not continuous, produced significant disturbances in behaviour with an increase in drinking, grooming and resting, and a reduction in rearing, jumping-play and locomotor activity. Furthermore, CO2 exposure was accompanied by increased plasma levels of corticosterone, suggesting that prolonged exposure to CO2 was stressful. The muscular structure can also be modified also when respiratory working conditions change. The expression of myosin heavy chain was significantly affected in the diaphragm and oral respiratory muscles: Masseter Superficialis and Anterior Digastric. Modified behaviour and hormonal changes both appear to be at the origin of the observed muscular adaptation.
Assuntos
Comportamento Animal/fisiologia , Dióxido de Carbono/toxicidade , Corticosterona/sangue , Corticosterona/metabolismo , Atividade Motora/fisiologia , Músculos Respiratórios/metabolismo , Poluição do Ar , Animais , Feminino , Cadeias Pesadas de Miosina/metabolismo , Distribuição Aleatória , Ratos Wistar , Estresse Psicológico/sangueRESUMO
Many songbirds are socially monogamous but genetically polyandrous, mating with individuals outside their pair bonds. Extra-pair paternity (EPP) varies within and across species, but reasons for this variation remain unclear. One possible source of variation is population genetic diversity, which has been shown in interspecific meta-analyses to correlate with EPP but which has limited support from intraspecific tests. Using eight populations of the genetically polyandrous red-winged blackbird (Agelaius phoeniceus), including an island population, we investigated whether population-level differences in genetic diversity led to differences in EPP. We first measured genetic diversity over 10 microsatellite loci and found, as predicted, low genetic diversity in the island population. Additional structure analyses with multilocus genotypes and mtDNA showed the island population to be distinct from the continental populations. However, the island population's EPP rate fell in the middle of the continental populations' distribution, whereas the continental populations themselves showed significant variation in EPP. This result suggests that genetic diversity by itself is not a predictor of EPP rate. We discuss reasons for the departure from previous results, including hypotheses for EPP that do not solely implicate female-driven behaviour.
Assuntos
Variação Genética , Paternidade , Aves Canoras/fisiologia , Animais , DNA/genética , Feminino , Masculino , Aves Canoras/genéticaRESUMO
Functional single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) (rs28493229) and caspase-3 (CASP3) (rs113420705; formerly rs72689236) are associated with susceptibility to Kawasaki's disease (KD). To evaluate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) unresponsiveness, we investigated 204 Japanese KD patients who received a single IVIG dose of 2 g kg(-1) (n=70) or 1 g kg(-1) daily for 2 days (n=134). The susceptibility allele of both SNPs showed a trend of overrepresentation in IVIG non-responders and, in combined analysis of these SNPs, patients with at least 1 susceptible allele at both loci had a higher risk for IVIG unresponsiveness (P=0.0014). In 335 prospectively collected KD patients who were treated with IVIG (2 g kg(-1)), this 2-locus model showed a more significant association with resistance to initial and additional IVIG (P=0.011) compared with individual SNPs. We observed a significant association when all KD patients with coronary artery lesions were analyzed with the 2-locus model (P=0.0031). Our findings strongly suggest the existence of genetic factors affecting patients' responses to treatment and the risk for cardiac complications, and provide clues toward understanding the pathophysiology of KD inflammation.
Assuntos
Caspase 3/genética , Vasos Coronários/patologia , Imunoglobulinas Intravenosas/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Alelos , Povo Asiático/genética , Criança , Vasos Coronários/enzimologia , Resistência a Medicamentos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/enzimologia , Polimorfismo de Nucleotídeo Único , Estudos ProspectivosRESUMO
Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry. Most cri-du-chat syndrome cases result from a sporadic de novo deletion that is associated with a low recurrence risk. On rare occasions, however, cri-du-chat syndrome with 5p monosomy can be accompanied by 5q trisomy. This combination is virtually always associated with parental large pericentric inversions. Among previously reported cri-du-chat syndrome cases with 5p monosomy accompanied by 5q trisomy, the aneusomy of chromosome 5 in all but one case was cytogenetically visible using G-banding. When an accompanying 5q trisomy is detected, a significant recurrence risk is expected. We here report on a patient with cri-du-chat syndrome phenotype who initially exhibited a normal karyotype on G-banding but in whom molecular analysis using multiplex ligation-dependent probe amplification and array comparative genomic hybridization revealed a 5p deletion accompanied by a 5q duplication. Parental chromosomal testing led to the identification of a very large pericentric inversion, of which breakpoints resided at the terminal regions of 5p15.31 and 5q35.1. This information was vital for counseling the family regarding the significantly high recurrence risk.
RESUMO
As antibiotic pressure often triggers bacterial resistance, the use of short-duration therapies is increasingly recommended. The objective of the present study was to evaluate both the clinical efficiency and the impact on oral streptococci of a 3 day versus a 7 day amoxicillin therapy for odontogenic infection requiring tooth extraction. On day 0, patients were randomly assigned to a 3 day or 7 day amoxicillin treatment. The tooth was extracted on day 2 and the post-operative follow-up was carried out on day 9. Oral flora was collected on days 0, 9 and 30, and the susceptibility of the streptococci to amoxicillin was determined. The results showed that treatment with amoxicillin for 3 or 7 days had a similar clinical efficiency, and also induced similar selection of oral streptococci with reduced susceptibility to amoxicillin, suggesting that the selection of strains with reduced susceptibility to amoxicillin is a rapid phenomenon, appearing even with short-duration therapies.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Streptococcus/efeitos dos fármacos , Extração Dentária , Adulto , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Esquema de Medicação , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Adulto JovemAssuntos
Hidradenite/etiologia , Leucemia Mieloide/complicações , Síndromes Paraneoplásicas/etiologia , Doença Aguda , Antineoplásicos/uso terapêutico , Hidradenite/patologia , Humanos , Leucemia Mieloide/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/patologia , RecidivaRESUMO
BACKGROUND: Skin is an attractive target for gene therapy. However, low efficiency of gene transfection has been a major problem. Histone deacetylase (HDAC) inhibitors have been reported to increase transgene expression in malignant cells. OBJECTIVES: We have estimated how much HDAC inhibitors might increase transgene expression in HaCaT cells, normal human epidermal keratinocyte (NHEK) cells, normal human dermal fibroblast (NHDF) cells and also in stratified cultured epidermal sheets that mimic the structure of the skin. METHODS: After treatment with each HDAC inhibitor [trichostatin A, FK228 and cyclic hydroxamic acid-containing peptide 31 (CHAP31)], transient transgene expression in HaCaT, NHEK and NHDF cells and stratified cultured epidermal sheets was compared with that of respective controls without treatment. Reactivation of transgene expression using HDAC inhibitors in HaCaT cells stably expressing the transgene was also studied. RESULTS: All HDAC inhibitors equally increased transient transgene expression by 2-fold in NHEK cells, 20-fold in NHDF cells and 6-fold in HaCaT cells when compared with untreated cells. This augmented expression continued for 72 h in all cell lines maintained under each HDAC inhibitor. In cells stably expressing the transgene, only CHAP31 reactivated transgene expression. In stratified cultured epidermal sheets, CHAP31 most effectively improved transient transgene expression. CONCLUSIONS: HDAC inhibitors are most efficient at amplifying transient transgene expression in NHDF cells. This suggests that NHDF cells may be most suitable as transgene targets for transient gene transfection using HDAC inhibitors. Specific HDAC inhibitors may not prove so useful for treating genetic dermatoses requiring cells stably expressing the correct gene, but may be advantageous in treating nonhealing cutaneous wounds or cancer.
Assuntos
Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases , Pele/efeitos dos fármacos , Transgenes , Acetilação , Morte Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Histona Desacetilases/metabolismo , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Pele/metabolismo , TransfecçãoRESUMO
BACKGROUND: Epidermolysis bullosa simplex (EBS) comprises a group of hereditary bullous diseases characterized by intraepidermal blistering caused by mutations in either keratin gene, KRT5 or KRT14. Significant correlation between the position of mutations within these proteins and the clinical severity of EBS has been noted. A recent report showed EBS cases in Israel had unique genetic features compared with European or U.S.A. associated families, which suggests that the ethnic and geographical features of EBS patients may be different. OBJECTIVES: To assess the possibility that EBS may present with certain specific features in Japanese and Koreans and to identify additional EBS mutations for genotype/phenotype correlation. METHODS: EBS was clinically diagnosed and confirmed by transmission electron microscopic examination of a skin biopsy. Mutation analysis of KRT5 and KRT14 was performed by direct sequencing in 17 Japanese and two Korean EBS patients. RESULTS: We have identified six novel KRT5 missense mutations (V143D, D158V, V186M, Q191P, R352S, G517D). R352S is the first mutation in the 2A domain. Most of these novel mutations changed amino acids that were evolutionarily conserved. Eight including all five mutations in EBS-Dowling-Meara patients have been previously reported. We were unable to detect mutations in five sporadic EBS-Koebner patients. The proportion of mutations in KRT5 (11 of 14; 78%) is higher than that for KRT14 mutations (3 of 14; 21%) in these Japanese and Korean EBS patients. CONCLUSIONS: Japanese and Korean patients with EBS showed very similar phenotype and genotype correlations with patients from Western countries. Whether the higher proportion of KRT5 mutations is a definite characteristic of Japanese and Korean patients with EBS or not, requires further research into mutations in Japanese and Korean people.
Assuntos
Epidermólise Bolhosa Simples/genética , Adulto , Sequência de Aminoácidos , Criança , Análise Mutacional de DNA/métodos , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Japão , Queratina-14/genética , Queratina-5/genética , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Mutação de Sentido Incorreto , FenótipoRESUMO
BACKGROUND: The major problem in cord blood (CB) transplantation for adult patients is shortage of stem cell number. To overcome this disadvantage, several studies on ex vivo expansion have been performed. However, such efforts are always troubled by the lack of a reliable and simple assay system for stem cells. Our aim was to establish an in vivo assay system to compare the directly repopulating ability of two populations of human hematopoietic stem cells using a xenogeneic transplant system. METHODS: Thirty CB samples from infants of each sex were pooled and enriched for CD34(+) progenitor cells. Enriched CD34(+) cells were transplanted into irradiated NOD/SCID mice at different male to female ratios, and human hematopoietic cells recovered 7 weeks after transplantation were analyzed by a quantitative DNA sex test using competitive PCR for the amelogenin gene. Using this assay system, ex vivo cultured and non-cultured CB cells were compared for repopulating ability. RESULTS: The sex ratio of human CB cells transplanted was found to be maintained for 7 weeks in matured and progenitor cells. The competitive repopulation assay of cultured and non-cultured CB cells showed a marked defect in the repopulating ability of cultured cells, although the LTCIC count was maintained during cultivation. DISCUSSION: Our assay system is a simple and reliable quantitative method that permits direct comparison of two stem cell compartments. The assay system will be useful for the assessment of the functional abilities of various human hematopoietic stem cells.
Assuntos
Bioensaio/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Células-Tronco Hematopoéticas/fisiologia , Camundongos Endogâmicos NOD , Camundongos SCID , Adulto , Animais , Células Cultivadas , Feminino , Células-Tronco Hematopoéticas/citologia , Humanos , Masculino , Camundongos , Transplante HeterólogoRESUMO
Leuprorelin acetate, an agonist of gonadotropin-releasing hormone (GnRH), is indicated in the treatment of prostate cancer. Recently, depot formulations of leuprorelin acetate have been widely used. We report three patients who showed a granulomatous reaction after treatment using a leuprorelin acetate 3-month depot formulation. These patients presented with 5-6-cm subcutaneous nodules at injection sites, which developed after the depot type was changed from a 1-month to a 3-month formulation. Skin biopsy showed epithelioid cells and foreign body giant cells containing round, translucent microspheres which formed sarcoidal granulomas. Changing to other GnRH agonists resulted in no further problems. We have reviewed the previous reports of leuprorelin acetate-induced granuloma formation. The formation of such granulomas may be related to the polymers that allow slow release after injection, or leuprorelin acetate itself may be responsible. The depot injection methods using leuprorelin also seem to have a causal effect in granuloma formation. Dermatologists need to know that depot leuprorelin acetate may cause a granulomatous reaction which produces a subcutaneous nodule that might be misdiagnosed as a malignant tumour.
Assuntos
Antineoplásicos Hormonais/efeitos adversos , Granuloma/induzido quimicamente , Leuprolida/efeitos adversos , Dermatopatias/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Preparações de Ação Retardada , Granuloma/patologia , Humanos , Injeções Subcutâneas , Masculino , Neoplasias da Próstata/tratamento farmacológico , Dermatopatias/patologiaRESUMO
Although Wilm's Tuomor gene (WT1) was first identified as a tumor suppressor gene for Wilm's tumor, WT1 overexpression has been detected in different malignant cell types including leukemia. Increased expression of WT1 in acute leukemia is potentially used as a marker of minimal residual disease. However, the significance of the gene for multiple myeloma is still not clear. To determine the clinical relevance of WT1 expression in multiple myeloma, we examined the association of clinical parameters and WT1 expression in bone marrow for 17 newly diagnosed multiple myeloma patients. WT1 was assessed by real-time quantitative polymerase chain reaction (RQ-PCR) and calculated standardized WT1 expression level per 100 plasma cells in the bone marrow specimen as "corrected WT1". The expression of standardized WT1 and corrected WT1 in myeloma was 59 to 1,600 copies/microg RNA and 0.05 to 406.3 copies/microg RNA/100 plasma cells, respectively, lower than in leukemia. WT1 transcripts increased when clinical factors worsen, including the stage, amount of M protein, Hb, platelet count, blood urea nitrogen (BUN), creatinine, serum alkaline phosphatase (ALP), calcium, beta2-microglobulin, thymidine kinase activity (TK), and C-reactive protein (CRP). In conclusion, the expression level of WT1 could be an additional marker to the standard parameters considered in risk assessment for multiple myeloma.
Assuntos
Biomarcadores Tumorais/análise , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteínas WT1/biossíntese , Medula Óssea/metabolismo , Expressão Gênica , Humanos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
While beta 2-microglobulin amyloidosis occurring in patients undergoing long-term dialysis is frequently associated with joint involvement, skin lesions have rarely been encountered. We report a 57-year-old man with extensive subcutaneous amyloid deposition forming large nodules on the buttocks; the patient had been on maintenance dialysis for 28 years. Although this condition is rare, a review of the literature indicates that the majority of such lesions occur around the buttock region.
Assuntos
Amiloidose/etiologia , Diálise Renal/efeitos adversos , Dermatopatias/etiologia , Amiloidose/diagnóstico , Nádegas , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Dermatopatias/diagnósticoRESUMO
Forty-nine multiflorane-type triterpenoids consisting of 11 compounds isolated from the seeds of Trichosanthes kirilowii (Cucurbitaceae) and 38 of their derivatives have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in Raji cells as a primary screening test for anti-tumor promoters. All of the compounds tested showed an inhibitory effect against EBV-EA activation, and among which 43 were revealed to possess remarkable activity with potencies either comparable to or stronger than that of glycyrrhetic acid, a known natural anti-tumor promoter. Their structure-activity relationship is discussed. Evaluation of the cytotoxic activity of karounidiol (27) against human cancer cell lines exhibited cytotoxicity especially against a human renal cancer.
Assuntos
Anticarcinógenos/farmacologia , Neoplasias/prevenção & controle , Triterpenos/farmacologia , Anticarcinógenos/química , Antígenos Virais/metabolismo , Cucurbitaceae/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Sementes/química , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/farmacologia , Triterpenos/química , Células Tumorais CultivadasRESUMO
Taraxastane, oleanane, ursane, lupane, taraxane, cycloartane, dammarane and tirucallane triterpenoids isolated from flowers of Compositae plants have been previously reported to exhibit anti-inflammatory effects and are variously competitive and non-competitive inhibitors of the serine proteases trypsin and chymotrypsin. The general features of those triterpenoids found to be protease inhibitors are having a hydroxy group and an appropriate side chain in the region of the molecule distal to the 3-hydroxy group. However, fatty acid esterification of the triterpenoid 3-hydroxy group can have a marked effect on inhibitor effectiveness. This suggests a possible means of rapid alteration of the plant defensive complement in vivo and of the bioactivity of these anti-inflammatory compounds.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Asteraceae/química , Quimotripsina/efeitos dos fármacos , Triterpenos/farmacologia , Inibidores da Tripsina/farmacologia , Tripsina/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Triterpenos/química , Inibidores da Tripsina/químicaRESUMO
Two phase III studies with tamsulosin, a selective alpha1A-adrenergic receptor antagonist, were conducted to evaluate the safety and efficacy of the standard treatment doses of 0.4 mg/day and 0.8 mg/day in patients with symptoms of benign prostatic hyperplasia (BPH). These large-scale clinical trials were the first to include extensive testing for possible drug-induced orthostatic hypotension (OH). The frequency of positive orthostatic tests and magnitude of vital sign changes were compared among tamsulosin and placebo-treated groups. The results indicate that tamsulosin up to 0.8 mg/day does not induce higher risk of OH than that of placebo. Data from post-marketing surveillance (PMS) studies of tamsulosin indicate that the incidence of hypotension and syncope is extremely low in community-dwelling elderly men treated for BPH. From the results of the phase III studies, PMS studies and an active-controlled clinical pharmacology study, we conclude that the orthostatic test is a useful and convenient method to evaluate the risk of OH and syncope during the investigational stage.
Assuntos
Antagonistas Adrenérgicos alfa/efeitos adversos , Hipotensão Ortostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Sulfonamidas/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1 , Ensaios Clínicos Fase III como Assunto , Humanos , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Adrenérgicos alfa 1 , TansulosinaRESUMO
Liposomes composed of hydrogenated egg phosphatidylcholine (HEPC) and cholesterol (CHOL) were found to activate the rat complement (C) system in a CHOL content-dependent manner. Liposomes containing 22 or 33 mol% CHOL activated the C system in a Ca(2+)-dependent manner, suggesting that C activation occurred via the classical pathway. Liposomes containing 44 mol% CHOL activated the C system in a Ca(2+) independent manner, suggesting that C activation occurred via the alternative pathway. The CHOL content appeared to dictate the pathway by which the C system was activated. This C activation was inhibited by removal of serum component(s), which adsorb to the liposomes. Activation of the alternative pathway, induced by the liposomes, was reduced by the depletion of IgG and IgM, whereas the classical pathway activation was reduced by the depletion of IgG, but not IgM. In addition, the removal of adsorbed serum component(s) by treatment with 44 mol% CHOL-containing liposomes decreased serum IgG and IgM levels that adsorb to the same liposomes, whereas the removal of adsorbed serum component(s) by treatment with 22 mol% CHOL-containing liposomes only slightly decreased serum IgG levels, which adsorbs to the same liposomes. Collectively, both IgG and IgM, which are specifically adsorbed to the liposomes in a CHOL-content dependent manner, were responsible for C activation via the alternative pathway induced by the 44 mol% CHOL containing liposomes. IgG alone would be partially responsible for C activation via the classical pathway induced by 22 or 33 mol% CHOL-containing liposomes. The discovery of this unique C-activating property of liposomes will be of value in attempts to decipher the underlying mechanism of C activation by providing a useful model membrane system.
Assuntos
Colesterol/análise , Via Alternativa do Complemento , Via Clássica do Complemento , Lipossomos , Fosfatidilcolinas/análise , Animais , Proteínas Sanguíneas/metabolismo , Ensaio de Imunoadsorção Enzimática , Immunoblotting , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Lipossomos/química , Masculino , Organofosfatos/metabolismo , Ratos , Ratos WistarRESUMO
Fifty-five triterpenoids consisting of 19 tetracyclic, 32 pentacyclic, and 4 incompletely cyclized triterpenoids, and 2 sterols, mostly isolated from various plant and fungal materials, were examined for their inhibitory effects on a purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Twenty triterpenoids and one sterol showed inhibitory effects with 50% inhibition concentration (IC50) values less than 5.0 microM. Among these cycloartenol ferulate (IC50 = 2.2 microM), 24-methylenecycloartanol ferulate (1.9 microM), lupenone (2.1 microM), betulin diacetate (1.4 microM), and karounidiol 29-benzoate (2.2 microM) inhibited most effectively. Some of the triterpenoids and sterols may be potential new lead compounds to find still more potent HIV-1 reverse transcriptase inhibitors.