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PURPOSE: To evaluate the effectiveness of standard corneal collagen crosslinking for children with progressive keratoconus. METHODS: Prospective study including 26 eyes of 26 patients younger than 18 years old with progressive keratoconus at Oftalmosalud Instituto de Ojos, Lima, Peru. Standard epi-off corneal crosslinking was performed in all eyes between January 2012 and January 2013. Pre- and postoperative evaluation (at 3 years) included uncorrected and best-corrected visual acuity and Scheimpflug analysis. Crosslinking failure was defined as an increase in maximum keratometry (Kmax) of more than 1 diopter after 1 year or more. RESULTS: Mean uncorrected visual acuity improvement was 0.24 LogMAR (p = 0.07) and mean best-corrected visual acuity improvement was 0.18 LogMAR (p = 0.01). None of the eyes lost more than one line in the best-corrected visual acuity. Four eyes (15.38%) lost two lines in the uncorrected visual acuity at 3 years postoperative. Mean steeper keratometry improvement was 1.14 diopters (p = 0.60). Progression rate was 23.07%. CONCLUSION: Standard epi-off corneal collagen crosslinking is safe and effective to halt the progression of the keratoconus with significant improvement in the best-corrected visual acuity at 3-year follow-up.

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Neutral lipids-involved in many cellular processes-are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2-10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles.

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The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L. alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP). [14C]Acetate was used as radioactive precursor for assays. Lipid analyses were performed by thin-layer and capillary gas chromatography, lipid droplets analyzed by fluorescence microscopy, and HMGCR levels determined by Western blot. In both cell lines, all four chemotypes exerted hypocholesterogenic effects within a concentration range of 3.2-32 µg/mL. Nonsaponifiable lipids manifested a decrease in incorporation of [14C]acetate into squalene, lanosterol, lathosterol, and cholesterol, but not into ubiquinone, thus suggesting an inhibition of enzymes in the MP downstream from farnesyl pyrophosphate. The tagetenone chemotype, the most efficacious hypocholesterogenic L. alba EO, lowered HMGCR protein levels; inhibited triacylglycerols, cholesteryl esters, and phospholipids synthesis; and diminished lipid droplets in size and volume. These results revealed that L. alba EOs inhibited different lipogenic pathways and such lipid-lowering effects could prove essential to prevent cardiovascular diseases.

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BACKGROUND: Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. HYPOTHESIS/PURPOSE: We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. STUDY DESIGN/METHODS: NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [(14)C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR-the rate-limiting step in cholesterol biosynthesis-along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. RESULTS: Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total-lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. CONCLUSIONS: The following mechanisms may have mediated the decrease in plasma lipids levels in mice: a down-regulation of hepatocyte-cholesterol synthesis occurred as a result of decreased HMGCR protein levels and catalytic activity; the levels of LDLR mRNA became elevated, thus suggesting an increase in the uptake of serum LDL, especially by the liver; and TG synthesis became reduced very likely because of a decrease in fatty-acid synthesis.

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Geraniol (G)-a natural compound present in the essential oils of many aromatic plants-has attracted interest for its potential antitumor effects. The molecular mechanisms of the growth inhibition and apoptosis induced by G in cancer cells, however, remain unclear. In this study, we investigated the effects of G on cell proliferation in culture in A549 cells and in vivo in those same tumor cells implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We demonstrated that G caused a dose- and time-dependent growth inhibition of A549 cells and tumor growth in vivo along with an induction of apoptosis. Moreover, further in vivo assays indicated that G decreased the levels of 3-hydroxymethylglutarylcoenzyme-A reductase-the rate-limiting enzyme in cholesterogenesis-in a dose-dependent manner along with cholesterogenesis and cholesterolemia in addition to reducing the amount of membrane-bound Ras protein. These results showed that the doses of G used in this work, though nontoxic to animals, clearly inhibited the mevalonate pathway, which is closely linked to cell proliferation and increased apoptosis in A549 tumors, but not in normal mouse-liver cells. Accordingly, we suggest that G displays significant antitumor activity and should be a promising candidate for cancer chemotherapy.

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Las estatinas son inhibidores competitivos de la 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA) reductasa ampliamente usados en los tratamientos contra las hipercolesterolemias. Los monoterpenos son componentes no nutritivos de la dieta presentes en aceites esenciales de varias plantas que han demostrado tener múltiples efectos en la vía del mevalonato. Se estudia el efecto y mecanismo de acción de monoterpenos presentes en aceites esenciales, así como la combinación de éstos entre sí y con simvastatina sobre la síntesis de colesterol, el metabolismo lipídico y la proliferación celular in vitro en células hepáticas Hep G2 y no hepáticas A549, e in vivo en ratones atímicos huéspedes y no huéspedes de tumores derivado de células A549 implantados en ellos. Se abre así una gran expectativa sobre la potencialidad de la administración conjunta de distintos monoterpenos y de extractos naturales de aceites esenciales en el mejoramiento de las terapias antihipercolesterolemiantes y/o el tratamiento del cáncer, como así también en el potencial sinergismo con estatinas como una alternativa para disminuir las dosis efectivas y los efectos indeseados y/o tóxicos.(AU)

Statins are competitive inhibitors of HMG-CoA reductase used in hypercholesterolemic patients. Monoterpenes are non-nutritive dietary components found in the essential oils of many plants with pharmacologic effects on mevalonate metabolism. The study is centered on the effects and action mechanisms of the monoterpene components of essential oils and the combination of monoterpenes between them and combined with simvastatin on cholesterogenesis, lipid metabolism and cellular proliferation in vitro using two established cell lines, Hep G2 (derived from a human hepatoblastoma), A549 (derived from a human lung adenocarcinoma) and in vivo in no host and host nude mice carrying implanted tumors derived from A549. This opens up great expectations about the potential of co-administration of different natural isoprenoids and essential oils in improving anti-cholesterolemic therapies and/or cancer treatment as well as in the potential synergism with statins as an alternative to lower effective doses, decreasing the likelihood of undesired and/or toxic effects.(AU)

As estatinas sÒo inibidores competitivos da 3-hidroxi-3-metilglutaril - coenzima A (HMG-CoA) reductase amplamente utilizados nos tratamentos contra as hipercolesterolemias. Os monoterpenos sÒo componentes nÒo nutritivos da dieta encontrados em óleos essenciais de várias plantas que demonstraram ter múltiplos efeitos na via do mevalonato. Estudamos o efeito e o mecanismo de aþÒo de monoterpenos encontrados em óleos essenciais, bem como a combinaþÒo deles entre si e com sinvastatina sobre a síntese de colesterol, o metabolismo lipídico e a proliferaþÒo celular in vitro em células hepáticas Hep G2 e nÒo hepáticas A549 e in vivo em camundongos atímicos hospedeiros ou nÒo hospedeiros de tumores derivados de células A549 implantadas neles. Isto abre grandes expectativas sobre o potencial da co-administraþÒo de diferentes monoterpenos e de extratos naturais de óleos essenciais na melhoria das terapias anti-hipercolesterolemiantes e/ou tratamento do cÔncer, assim como no potencial sinergismo com estatinas como uma alternativa para reduzir as doses efetivas e os efeitos indesejáveis e/ou tóxicos.(AU)

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Las estatinas son inhibidores competitivos de la 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA) reductasa ampliamente usados en los tratamientos contra las hipercolesterolemias. Los monoterpenos son componentes no nutritivos de la dieta presentes en aceites esenciales de varias plantas que han demostrado tener múltiples efectos en la vía del mevalonato. Se estudia el efecto y mecanismo de acción de monoterpenos presentes en aceites esenciales, así como la combinación de éstos entre sí y con simvastatina sobre la síntesis de colesterol, el metabolismo lipídico y la proliferación celular in vitro en células hepáticas Hep G2 y no hepáticas A549, e in vivo en ratones atímicos huéspedes y no huéspedes de tumores derivado de células A549 implantados en ellos. Se abre así una gran expectativa sobre la potencialidad de la administración conjunta de distintos monoterpenos y de extractos naturales de aceites esenciales en el mejoramiento de las terapias antihipercolesterolemiantes y/o el tratamiento del cáncer, como así también en el potencial sinergismo con estatinas como una alternativa para disminuir las dosis efectivas y los efectos indeseados y/o tóxicos.

Statins are competitive inhibitors of HMG-CoA reductase used in hypercholesterolemic patients. Monoterpenes are non-nutritive dietary components found in the essential oils of many plants with pharmacologic effects on mevalonate metabolism. The study is centered on the effects and action mechanisms of the monoterpene components of essential oils and the combination of monoterpenes between them and combined with simvastatin on cholesterogenesis, lipid metabolism and cellular proliferation in vitro using two established cell lines, Hep G2 (derived from a human hepatoblastoma), A549 (derived from a human lung adenocarcinoma) and in vivo in no host and host nude mice carrying implanted tumors derived from A549. This opens up great expectations about the potential of co-administration of different natural isoprenoids and essential oils in improving anti-cholesterolemic therapies and/or cancer treatment as well as in the potential synergism with statins as an alternative to lower effective doses, decreasing the likelihood of undesired and/or toxic effects.

As estatinas são inibidores competitivos da 3-hidroxi-3-metilglutaril - coenzima A (HMG-CoA) reductase amplamente utilizados nos tratamentos contra as hipercolesterolemias. Os monoterpenos são componentes não nutritivos da dieta encontrados em óleos essenciais de várias plantas que demonstraram ter múltiplos efeitos na via do mevalonato. Estudamos o efeito e o mecanismo de ação de monoterpenos encontrados em óleos essenciais, bem como a combinação deles entre si e com sinvastatina sobre a síntese de colesterol, o metabolismo lipídico e a proliferação celular in vitro em células hepáticas Hep G2 e não hepáticas A549 e in vivo em camundongos atímicos hospedeiros ou não hospedeiros de tumores derivados de células A549 implantadas neles. Isto abre grandes expectativas sobre o potencial da co-administração de diferentes monoterpenos e de extratos naturais de óleos essenciais na melhoria das terapias anti-hipercolesterolemiantes e/ou tratamento do câncer, assim como no potencial sinergismo com estatinas como uma alternativa para reduzir as doses efetivas e os efeitos indesejáveis e/ou tóxicos.

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Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitumor activity against several cell lines. We investigated the effects of geraniol on lipid metabolic pathways involved in Hep-G2 cell proliferation and found that geraniol inhibits the mevalonate pathway, phosphatidylcholine biosynthesis, cell growth, and cell cycle progression (with an arrest occurring at the G0/G1 interphase) and increases apoptosis. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in cholesterol synthesis, was inhibited at the transcriptional and posttranscriptional levels, as assessed by real-time RT-PCR, Western blots, and [(14)C]HMG-CoA-conversion radioactivity assays. That geraniol decreased cholesterogenesis but increased the incorporation of [(14)C]acetate into other nonsaponifiable metabolites indicated the existence of a second control point between squalene and cholesterol involved in redirecting the flow of cholesterol-derived carbon toward other metabolites of the mevalonate pathway. That exogenous mevalonate failed to restore growth in geraniol-inhibited cells suggests that, in addition to the inhibition of HMGCR, other dose-dependent actions exist through which geraniol can impact the mevalonate pathway and consequently inhibit cell proliferation. These results suggest that geraniol, a nontoxic compound found in many fruits and herbs, exhibits notable potential as a natural agent for combatting cancer and (or) cardiovascular diseases.

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Introducción. La neumología intervencionista es un campo que se impone cada vez más en el mundo, y necesita el concurso de la anestesia. Se pretende mostrar la experiencia reunida en un centro hospitalario durante un año en el manejo anestésico de este tipo de procedimientos. Métodos. Estudio descriptivo de serie de casos. Resultados. Durante un año se llevaron a cabo 16 procedimientos en 14 pacientes, en un mismo centro. Se practicaron biopsias transbronquiales, fotocoagulación y plastias neumáticas, con inserción de stents traqueales y bronquiales. Las técnicas anestésicas fueron diversas: desde la anestesia local y la sedación superficial hasta la anestesia general, con medicamentos de uso común en nuestro medio. No se presentaron complicaciones mayores. Discusión. Se discuten las técnicas anestésicas empleadas comparándolas con las reportadas en la literatura mundial, las complicaciones y las limitaciones del estudio. Conclusiones. La anestesia para procedimientos de neumología intervencionista es variable, adaptada a las condiciones del paciente, buscando mantener la seguridad de este, y concertada con el neumólogo tratante.

Introduction. Interventional pulmonology is an increasingly popular area around the world and requires anesthesia. The objective is to share theexperience accumulated at a hospital center in one year of anesthesia management for this type of procedures.Methods. Case series study. Results. 16 procedures were performed in 14patients in one year, at the same institution. The procedures included transbronchial biopsies, photocoagulation and pneumatic-plasty with insertion of tracheal and bronchial stents. The anesthetic techniques were varied and included local anesthesia and superficial sedation as well as general anesthesia with agents commonlyused in our environment. No serious complications occurred. Discussion. The anesthesia techniques used are discussed and compared against those reported in the world literature, as well as the complications and limitations of the study.

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