RESUMO
Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.
Assuntos
Diabetes Gestacional/metabolismo , Leucotrieno B4/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Pulmão/metabolismo , PPAR alfa/metabolismo , PPAR gama/metabolismo , Prostaglandina D2/análogos & derivados , Animais , Diabetes Gestacional/genética , Feminino , Feto/embriologia , Feto/metabolismo , Ligantes , Pulmão/química , Pulmão/embriologia , Masculino , Azeite de Oliva , PPAR alfa/genética , PPAR gama/genética , Óleos de Plantas/metabolismo , Gravidez , Prostaglandina D2/metabolismo , Ratos , Ratos Wistar , Óleo de Cártamo/metabolismoRESUMO
The purpose of this study was to determine whether current HAART use is associated with recent sexual intercourse among HIV-infected women (18-49 years) from Brazil, South Africa and Uganda. We conducted an analysis of survey data from a cross-sectional study, which enrolled 179 HIV-infected women receiving regular care from the Mbarara Hospital HIV Clinic in Uganda (n=85); the Perinatal HIV Research Unit in Soweto, South Africa (n=50); and the IPEC-Fiocruz cohort in Rio de Janeiro, Brazil (n=44). The primary outcome was sexual intercourse in the previous month. Secondary outcomes were protected sex and contraceptive use. We found that overall, 46% reported recent sexual intercourse. After adjusting for covariates, recent sexual intercourse was not associated with HAART use (AOR: 0.76; 95%CI: 0.34-1.72); however, it was significantly associated with being currently married, wanting to have more children and having higher HAART optimism. Among women reporting recent sexual intercourse (n=83), HAART users were significantly more likely to practice protected sex (crude OR: 3.64; 95%CI: 1.41-9.38) and non-significantly more likely to use contraceptive methods (crude OR: 2.15; 95%CI: 0.77-5.99). In summary, self-reported recent sexual intercourse is not more likely among women on HAART. Moreover, sexually active HAART users may be more likely to practice protected sex and use contraceptives.
Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Comportamento Sexual , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade/psicologia , Brasil , Comportamento Contraceptivo/psicologia , Estudos Transversais , Feminino , Infecções por HIV/psicologia , Humanos , Pessoa de Meia-Idade , Análise de Regressão , África do Sul , UgandaRESUMO
Four macrocyclic trichothecenes, roridin A, roridin E, verrucarin A and verrucarin J, produced by the hypocrealean epibiont of Baccharis coridifolia, were evaluated for their inhibitory activity against the arenavirus Junin (JUNV), the etiological agent of Argentine hemorrhagic fever. The trichothecenes achieved a dose-dependent inhibition of JUNV multiplication at concentrations not affecting cell viability. The 50 % inhibitory concentration (IC50) values determined by a virus yield inhibition assay were in the range 1.2 - 4.9 ng/ml. The most active compound was verrucarin J which reduced JUNV yield more than 2 log units and had a similar effect against the arenavirus Tacaribe. The trichothecenes lacked virucidal effects on JUNV virions. From time of addition and removal experiments, it can be concluded that verrucarin J inhibited a late stage in the replicative cycle of JUNV, after 5 h of adsorption.
Assuntos
Antivirais/farmacologia , Asteraceae/virologia , Vírus Junin/efeitos dos fármacos , Tricotecenos/farmacologia , Animais , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Vírus Junin/crescimento & desenvolvimento , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Tricotecenos/química , Células VeroRESUMO
Two new trisulfated triterpene glycosides, liouvillosides A (1) and B (2), have been isolated from the Antarctic sea cucumber Staurocucumis liouvillei. Their structures have been elucidated by spectroscopic analysis (NMR and FABMS) and chemical transformations. Liouvillosides A (1) and B (2) are two new examples of a small number of trisulfated triterpene glycosides from sea cucumbers belonging to the family Cucumariidae. Both glycosides were found to be virucidal against herpes simplex virus type 1 (HSV-1) at concentrations below 10 microg/mL.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Oligossacarídeos/isolamento & purificação , Pepinos-do-Mar/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antivirais/isolamento & purificação , Configuração de Carboidratos , Chlorocebus aethiops , Ensaios de Seleção de Medicamentos Antitumorais , Herpesvirus Humano 1/efeitos dos fármacos , Hidrólise , Espectroscopia de Ressonância Magnética , Metilação , Testes de Sensibilidade Microbiana , Oligossacarídeos/química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Células VeroRESUMO
Disodium 3beta,21-dihydroxypregn-5-en-20-one disulfate (2), sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3), sodium 3beta,21-dihydroxypregn-5-en-20-one 21-sulfate (4), and disodium 3beta,6alpha-dihydroxy-5alpha-pregnan-20-one disulfate (6) have been synthesized and completely characterized for the first time from readily available materials. Sulfation was performed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. Selective sulfation of 3beta,21-dihydroxypregn-5-en-20-one rendered sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3) as the major compound. The synthetic sulfated steroids as well as natural disulfated polyhydroxysteroids (7-9) isolated by us from the antarctic ophiuroid Astrotoma agassizii and the synthetic derivatives disodium 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene 3-acetate, 2,21-disulfate (7a) and 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene (7b) were comparatively evaluated for their inhibitory effect on the replication of one DNA (HSV-2) and two RNA (PV-3, JV) viruses. In general, steroids with sulfate groups at C-21 and C-2 or C-3 were the most effective in their inhibitory action against HSV-2 and also proved to be active against PV-3 and JV.
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Colesterol/análogos & derivados , Sulfatos/química , Animais , Morte Celular/efeitos dos fármacos , Chlorocebus aethiops , Colesterol/síntese química , Colesterol/farmacologia , Replicação do DNA/efeitos dos fármacos , Equinodermos/química , Herpesvirus Humano 2/efeitos dos fármacos , Vírus Junin/efeitos dos fármacos , Poliovirus/efeitos dos fármacos , Células Vero/efeitos dos fármacosRESUMO
From the water-insoluble lipid fraction of the methylene chloride/methanol extract of the starfish Cosmasterias lurida, two new glucosylceramides together with a known glucosylceramide, ophidiacerebroside E, were isolated by chromatographic procedures and characterized by spectroscopic (1H and 13C nuclear magnetic resonance, mass spectrometry) methods. The new compounds were identified as (2S,3R,4E,8E,10E)-1-(beta-D-glucopyranosyloxy)-3 -hydroxy-2-[(R)-2-hydroxyheptadecanoyl)amino]-9-methyl-4,8,10-o ctadecatriene (3) and (2S,3R,4E,8E,10E)-1-(beta-D-glucopyranosyloxy)-3 -hydroxy-2-[(R)-2-hydroxyoctadecanoyl)amino]-9-methyl-4,8,10-oc tadecatriene (4).
Assuntos
Glucosilceramidas/química , Glucosilceramidas/isolamento & purificação , Estrelas-do-Mar/química , Animais , Sequência de Carboidratos , Cromatografia Líquida de Alta Pressão , Dados de Sequência Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
One new and three known sulfated steroidal polyols have been isolated from the ophiuroid Ophioplocus januarii, collected at San Antonio Oeste, Río Negro, Argentina. The four compounds possess 4 alpha,11 beta-dihydroxy-3 alpha,21-disulfoxy substituents and the A/B cis ring junction but differ in the side chain. The new compound has been characterized as (22E)-5 beta-24-norcholest-22-ene-3 alpha,4 alpha,11 beta,21-tetrol 3,21-disulfate (4). The structures of the four compounds were determined from spectral data and comparison with those of related steroidal polyols. The four compounds were tested for their inhibitory effect on the replication of one DNA and three RNA viruses. Compounds 2 and 4 were active against respiratory syncytial and polio viruses, and compound 3 inhibited Junin virus, responsible for Argentine hemorrhagic fever.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Estrelas-do-Mar/química , Esteróis/isolamento & purificação , Replicação Viral/efeitos dos fármacos , Animais , Fármacos Anti-HIV/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Efeito Citopatogênico Viral/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Vírus de DNA/efeitos dos fármacos , Vírus de DNA/metabolismo , Vírus de RNA/efeitos dos fármacos , Vírus de RNA/metabolismo , Esteróis/farmacologiaRESUMO
INTRODUCTION: More than 97% of common bile duct stones can be successfully managed by endoscopic papillotomy, mechanical lithotripsy and extracorporeal shock-wave lithotripsy. In this study, we evaluate the role of laser lithotripsy after failure of the above mentioned endoscopic methods. PATIENTS AND METHODS: Eighteen patients (15F, 3M; median age = 69 (28-83) years) were treated by endoscopic laser lithotripsy after ESWL failure. We employed a Rhodamine-6 G laser with a stone-tissue recognizing system. The laser fibers were cholangioscopically (direct vision) or blindly (under plain fluoroscopic control) placed. RESULTS: Seventeen patients were treated endoscopically and one was successfully managed percutaneously after failure of the transpapillary approach. Fourteen (78%) were stone-free after a mean of 1.56 laser therapy sessions alone. Two additional patients were successfully managed after partial fragmentation with combined treatment (mechanical lithotripsy: n = 1, electrohydraulic lithotripsy: n = 1). Overall, 89% of the patients were freed from their calculi. Cholangitis occurred once and the mortality was zero. CONCLUSIONS: We conclude that laser lithotripsy is an effective and safe treatment alternative in a highly selected patient population with difficult bile duct stones and considerable surgical risk.
Assuntos
Cálculos Biliares/terapia , Litotripsia a Laser , Litotripsia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
Four new sulfated asterosaponins, designated as cosmasterosides A [1], B [2], C [4], and D [5], have been isolated from the Atlantic starfish Cosmasterias lurida along with large amounts of the pentaglycoside ophidianoside F [3] and the minor component forbeside H [6], previously isolated from Ophidiaster ophidianus and Asterias forbesi, respectively. Cosmasteroside A [1] contains the same oligosaccharide chain as ophidianoside F [3] and a (20S)-5 alpha-cholesta-9(11),24-diene-3 beta,6 alpha,20-triol-3 beta-sulfated aglycone. Cosmasterosides B [2], C [4], and D [5] are based on the known aglycone, thornasterol A, and differ in the number and type of monosaccharide components of the carbohydrate chain. Cosmasteroside B [2] contains a novel oligosaccharide chain that differs from that of ophidianoside F [3] by the replacement of the quinovose unit attached to C-6 of the steroidal aglycone by glucose. The tetraglycosides cosmasterosides C [4] and D [5] are structurally related to ophidianoside F [3] and cosmasteroside B [2], respectively, by the loss of a terminal fucose unit.
Assuntos
Glicosídeos/química , Oligossacarídeos/química , Saponinas/química , Estrelas-do-Mar/química , Animais , Sequência de Carboidratos , Feminino , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Ovário/químicaRESUMO
Two novel steroidal monoglycoside sulfates, luridosides A [1] and B [2], have been isolated from the starfish Cosmasterias lurida. These compounds co-occur with one known steroidal monoglycoside, pycnopodioside C [3]. The structures of the new metabolites were determined from spectral data and comparison with those of related steroids.