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Prensa méd. argent ; 105(3): 106-109, may 2019.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1025200


Contexto: La litiasis vesicular asintomática es un cuadro clínico cuyo abordaje terapéutico resulta controversial. Objetivos: Definir qué pacientes con litiasis vesicular son asintomáticos, identificar riesgos y beneficios de la conducta expectante en pacientes asintomáticos, mencionar qué grupos de pacientes asintomáticos se beneficia con la cirugía preventiva. Material y métodos: Se realizó una revisión de trabajos publicados en la plataforma. Pubmed para identificar y analizar aquellos que consideramos más representativos sobre litiasis vesicular asintomática, y así describir la conducta más apropiada ante dicha situación. Resultados: Al realizar la revisión de artículos con bajo nivel de evidencia (C-D) observamos que par la litiasis vesicular asintomática la conducta expectante es la más recomendada. Sin embargo varios trabajos hacen referencia a grupos de pacientes seleccionados que debido a su condición de base se beneficiarían con la cirugía. Conclusiones: Con la información obtenida de los artículos analizados se concluye que No está recomendada de forma rutinaria la colecistectomía profiláctica en los pacientes con litiasis asintomática; los pacientes que se benefician de la cirugía y en los cuales la indicación de colecistectomía es clara son: pacientes con riesgo elevado de desarrollar cáncer de vesícula (existencia de pólipos vesiculares con crecimiento rápido o mayor de 1 cm, vesícula en porcelana, cáculo mayor de 3 cm, mujer joven de origen ameroindio) y pacientes con mayor riesgo de desarrollar coplicaciones como son los jóvenes con anemia hemolítica crónica. El procedimiento quirúrgico iindicado es la colecistectomía por vía laparoscópica, siendo éste el procedimiento quirúrgico con menor tasa de morbimortalidad y mejor recuperarción postoperatoria disponibe (AU)

The presence of stones in the gallbladder is a condition relatively common in many parts of the world, being present in 10% to 15% of the adult population, and the presence of stones in the gallbladder afficts more than 21.9 % of the population of the city of Buenos Aires. When patients present with symptoms of biliary lithiasis, there is consense toward the surgical removal. But in the patients with asymptomatic gallstones that have no pain and do not have compications, the management of these silent gallstones is somewhat controversial. Data coupled with results suggesting that persons's life expectancy is not increased by prophylactic cholecystectomy, have discouraged surgical tratment of gallstones unless symptoms are present. The aim of this report was to determine which patients with biliary lithiasis should be considered as asymptomatic patients, and to consider which group of the expectant management in asymptomatic patients, and to consider which group of these patients can be beneficiated with a preventive cholecystectomy. A revision of the literature was performed, considering the management of the asymptomatic gallstone disease, whether if it should be preferable the expectant management or instead an active treatment. The expectant management was the mos recommended procedure fot these patients (AU)

Humanos , Cálculos Biliares/terapia , Colecistectomia Laparoscópica , Doenças Assintomáticas/terapia , Conduta Expectante
Nutrients ; 10(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513887


It has been well established that moderate alcohol consumption inversely correlates with cardiovascular morbidity and mortality, whereas binge alcohol drinking increases cardiovascular disease risk. The aim of this study was to assess in vivo the impact of different drinking patterns on reverse cholesterol transport (RCT); the atheroprotective process leading to the removal of excess cholesterol from the body. RCT was measured with a standardized, radioisotope-based technique in three groups of atherosclerosis-prone apolipoprotein E knock out mice: Placebo group, receiving water, which would mimic the abstainers; moderate group, receiving 0.8 g/kg alcohol/day for 28 days, which would mimic a moderate intake; binge group, receiving 0.8 g/kg alcohol/day for 5 days/week, followed by the administration of 2.8 g/kg alcohol/day for 2 days/week, which would mimic a heavy intake in a short period. Mice in the binge drinking group displayed an increase in total cholesterol, high density lipoprotein cholesterol (HDL-c) and non-HDL-c (all p < 0.0001 vs. placebo), and a significantly reduced elimination of fecal cholesterol. The moderate consumption did not lead to any changes in circulating lipids, but slightly improved cholesterol mobilization along the RCT pathway. Overall, our data confirm the importance of considering not only the total amount, but also the different consumption patterns to define the impact of alcohol on cardiovascular risk.

Consumo de Bebidas Alcoólicas , Colesterol/metabolismo , Etanol/administração & dosagem , Etanol/efeitos adversos , Animais , Apolipoproteínas E/metabolismo , Transporte Biológico/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
Angew Chem Int Ed Engl ; 54(25): 7386-90, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25950770


A direct aminocatalytic synthesis has been developed for the chemo-, regio-, diastereo-, and enantioselective construction of densely substituted polycyclic carbaldehydes containing fused cyclohexadiene rings. The chemistry utilizes, for the first time, remotely enolizable π-extended allylidenemalononitriles as electron-rich 1,3-diene precursors in a direct eliminative [4+2] cycloaddition with both aromatic and aliphatic α,ß-unsaturated aldehydes. The generality of the process is demonstrated by approaching 6,6-, 5,6-, 7,6-, 6,6,6-, and 6,5,6-fused ring systems, as well as biorelevant steroid-like 6,6,6,6,5- and 6,6,6,5,6-rings. A stepwise reaction mechanism for the key [4+2] addition is proposed as a domino bis-vinylogous Michael/Michael/retro-Michael reaction cascade. The utility of the malononitrile moiety as traceless activating group of the dicyano nucleophilic substrates is demonstrated.

Aldeídos/síntese química , Compostos Alílicos/química , Cicloexenos/química , Nitrilos/química , Compostos Policíclicos/síntese química , Aldeídos/química , Compostos Alílicos/síntese química , Catálise , Reação de Cicloadição , Cicloexenos/síntese química , Nitrilos/síntese química , Compostos Policíclicos/química , Estereoisomerismo
Arthritis Rheumatol ; 67(5): 1155-64, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25605003


OBJECTIVE: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti-tumor necrosis factor α agents in RA is considered secondary to their anti-inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high-density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol-loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The aim of this study was to investigate the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in RA patients and to study the in vitro effects of the two drugs on macrophage cholesterol handling. METHODS: Sera from RA patients treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before treatment, after 6 weeks of treatment, and after 6 months of treatment were analyzed for CEC and CLC by radioisotopic and fluorometric techniques, respectively. The influence of MTX and adalimumab on macrophage cholesterol efflux and uptake was evaluated in vitro using human THP-1-derived macrophages. RESULTS: MTX treatment was associated with increases in serum HDL, low-density lipoprotein, and total cholesterol levels and with ATP-binding cassette G1-mediated and scavenger receptor class B type I (SR-BI)-mediated increases in CEC; MTX treatment was not associated with modifications in CLC. Adalimumab treatment was associated with increases in serum HDL levels, a transient increase in SR-BI-mediated CEC, a transient decrease in ATP-binding cassette A1-mediated CEC, and a significant reduction in CLC; in addition, adalimumab reduced macrophage cholesterol uptake in vitro. CONCLUSION: Antiatherosclerotic activity associated with MTX and adalimumab may be mediated by beneficial and complementary effects on lipoprotein functions and on macrophage cholesterol handling. As a whole, these mechanisms may oppose foam cell formation.

Anticorpos Monoclonais Humanizados/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Aterosclerose/metabolismo , Colesterol/metabolismo , Macrófagos/efeitos dos fármacos , Metotrexato/farmacocinética , Adalimumab , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Feminino , Humanos , Técnicas In Vitro , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Receptores Depuradores Classe B
PLoS One ; 8(8): e71572, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23951193


Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the amount of radioactive sterols in the feces, independently on the expression of apolipoprotein E in the macrophages injected into recipient mice and in absence of changes of plasma levels of high density lipoprotein-cholesterol. Gene expression analysis revealed that cyclosporine A inhibited the hepatic levels of cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance of the last observation was challenged by the demonstration that mice treated or not with cyclosporine A showed the same levels of circulating beta-sitosterol. These results indicate that treatment of mice with cyclosporine A impaired the macrophage reverse cholesterol transport by reducing fecal sterol excretion, possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression. The current observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following the immunosuppressant therapy in organ transplanted recipients.

Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol/metabolismo , Ciclosporina/administração & dosagem , Macrófagos Peritoneais/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Transporte Biológico/efeitos dos fármacos , Colesterol 7-alfa-Hidroxilase/antagonistas & inibidores , Colesterol 7-alfa-Hidroxilase/genética , Fezes/química , Regulação da Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Cinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sitosteroides/sangue , Trítio