Pediatric patients with lysosomal acid lipase deficiency / Pacientes pediátricos con deficiencia de lipasa ácida lisosomal

Lysosomal acid lipase (LAL) deficiency is a rare, autosomal recessive disease caused by mutations in the LIPA gene, which produces cholesteryl ester and triglyceride accumulation predominantly in hepatocytes, adrenal glands, and gastrointestinal tract. We describe two new cases occurring in siblings, aged 5 and 7 years, who presented with hepatomegaly, dyslipidemia, and abnormal liver function. Percutaneous liver biopsy revealed portal inflammation, hypertrophic Kupffer cells with a foamy appearance and microvesicular steatosis with fibrosis. Immunostaining for lysosomal markers, cathepsin D and LAMP1 reflected the lysosomal nature of the lipid vacuoles. After enzymatic confirmation, enzyme replacement therapy was initiated for both siblings. Follow-up transaminase levels and lipid profiles showed a notable decrease in AST and ALT and a slight increase in HDL cholesterol. It is crucial to increase awareness of this rare condition among clinicians and pathologists. The expression of lysosomal markers around the lipid vacuoles might help diagnose LAL deficiency in pediatric patients.(AU)

La deficiencia de lipasa ácida lisosomal (LAL) es una enfermedad autosómica recesiva inusual, causada por mutaciones en el gen LIPA, que genera acumulación de éster de colesterol y triglicéridos predominantemente en hepatocitos, glándulas suprarrenales y tracto gastrointestinal. Describimos 2 casos adicionales que ocurrieron en 2 hermanos, de 5 y 7 años, que presentaron hepatomegalia, dislipidemia y función hepática anormal. La biopsia hepática percutánea reveló inflamación portal leve, células de Kupffer hipertróficas, con un aspecto espumoso y esteatosis microvesicular difusa con fibrosis. La inmunotinción de marcadores lisosomales, catepsina D y LAMP1, reflejó la naturaleza lisosomal de las vacuolas lipídicas. Después de la confirmación enzimática, ambos hermanos iniciaron terapia de reemplazo enzimático. Los niveles de transaminasas y los perfiles lipídicos de seguimiento mostraron una disminución notoria en AST y ALT y un ligero aumento en el colesterol HDL. Es crucial aumentar la conciencia de esta inusual condición entre médicos y patólogos. La expresión de marcadores lisosomales alrededor de las vacuolas lipídicas podría ayudar a diagnosticar la deficiencia de LAL en pacientes pediátricos.(AU)

Pediatric patients with lysosomal acid lipase deficiency.

Lysosomal acid lipase (LAL) deficiency is a rare, autosomal recessive disease caused by mutations in the LIPA gene, which produces cholesteryl ester and triglyceride accumulation predominantly in hepatocytes, adrenal glands, and gastrointestinal tract. We describe two new cases occurring in siblings, aged 5 and 7 years, who presented with hepatomegaly, dyslipidemia, and abnormal liver function. Percutaneous liver biopsy revealed portal inflammation, hypertrophic Kupffer cells with a foamy appearance and microvesicular steatosis with fibrosis. Immunostaining for lysosomal markers, cathepsin D and LAMP1 reflected the lysosomal nature of the lipid vacuoles. After enzymatic confirmation, enzyme replacement therapy was initiated for both siblings. Follow-up transaminase levels and lipid profiles showed a notable decrease in AST and ALT and a slight increase in HDL cholesterol. It is crucial to increase awareness of this rare condition among clinicians and pathologists. The expression of lysosomal markers around the lipid vacuoles might help diagnose LAL deficiency in pediatric patients.

Atualização em reações de hipersensibilidade aos anestésicos locais / Update on local anesthetics hypersensitivity reactions

Os anestésicos locais são essenciais em diversos procedimentos médicos e odontológicos. Funcionam estabilizando as membranas neuronais e inibindo a transmissão de impulsos neurais, o que permite a realização desses procedimentos com mais segurança e sem dor. As reações adversas a drogas são definidas pela Organização Mundial da Saúde como todos os efeitos nocivos, não intencionais e indesejáveis de uma medicação, que ocorrem em doses usadas para prevenção, diagnóstico e tratamento. As reações de hipersensibilidade são reações adversas do tipo B, imprevisíveis, que clinicamente se assemelham a reações alérgicas e podem ou não envolver um mecanismo imune. As reações de hipersensibilidade verdadeiras aos anestésicos locais são raras, apesar de superestimadas. Nesta revisão destacamos a necessidade de uma avaliação completa dos pacientes com suspeita de reação alérgica aos anestésicos locais, incluindo a investigação de outros possíveis alérgenos que tenham sido utilizados no procedimento, como analgésicos, antibióticos e látex. A estratégia de investigação e seleção de pacientes para testes deve se basear na história clínica. Dessa forma, poderemos fornecer orientações mais assertivas e seguras aos pacientes.

Local anesthetics are essential in many medical and dental procedures. They work by stabilizing neuronal membranes and inhibiting the transmission of neural impulses, which allows these procedures to be performed more safely and without pain. Adverse drug reactions are defined by the World Health Organization as all harmful, unintended and undesirable effects of a medication, which occur at doses used for prevention, diagnosis and treatment. Hypersensitivity reactions are unpredictable type B adverse reactions that clinically resemble allergic reactions and may or may not involve an immune mechanism. True hypersensitivity reactions to local anesthetics are rare, although overestimated. In this review, we highlight the need for a thorough evaluation of patients with suspected allergic reaction to local anesthetics, including investigation of other possible allergens that may have been used in the procedure, such as analgesics, antibiotics and latex. The investigation strategy and patient selection for testing should be based on clinical history. In this way, we will be able to provide more assertive and safe guidelines to patients.

Determination of lipids and fatty acids in infant formula: comparison of the conventional x direct method / Lipídios e ácidos graxos em fórmula infantil: comparação de metodologias de extração convencional x direta

Lipids in food are conventionally analyzed in two stages: extraction with organic solvent and fat esterification reaction, in this case, the type of fat of each food influences the choice of extraction and esterification reagents. In the direct method, such procedures are performed in one step. This work compared the conventional extraction method and quantification of lipids and fatty acids, with a direct method in infant formula. A reference sample of infant formula conteining certified lipids and fatty acids values from the National Institute of Standards and Technology was used. The conventional method for lipid analysis used the acid hydrolysis method; for the determination of fatty acids, the fats were extracted with a mixture of ethyl ether and petroleum ether. The direct method consisted of direct trans esterification with sodium methoxide. In the analysis of fatty acids, the majority of the results showed statistically equal values (α < 0.05) for both methods. The direct method proved suitable, mainly because of reduction in analytical time and quantity of solvents (AU).

Os lipídios em alimentos são analisados, de forma convencional, em duas etapas: extração com solvente orgânico e reação de esterificação da gordura, neste caso o tipo de gordura de cada alimento influencia na escolha dos reagentes da extração e esterificação. No método direto, estes procedimentos são realizados em uma etapa única. Este trabalho comparou a metodologia convencional de extração e quantificação de lipídios e ácidos graxos, com um método direto em fórmula infantil. Foi utilizada uma amostra de referência de fórmula infantil com valores certificados para lipídios e ácidos graxos da Nacional Institute of Standards and Technology. A metodologia convencional para a análise de lipídios empregou método com hidrólise ácida; para a determinação dos ácidos graxos, a gordura foi extraída com uma mistura de éter etílico e éter de petróleo. O método direto fundamentou-se na transesterificação direta com metóxido de sódio. Na análise dos ácidos graxos, a maioria dos resultados demonstrou valores estatisticamente iguais (α < 0,05) para os dois métodos. O método direto demonstrou ser apropriado, principalmente pela diminuição do tempo de análise e quantidade de solventes (AU).

Use of estradiol cypionate to induce ovulation in buffalo raised in floodplain areas of Itacoatiara, Amazonas / [Uso do cipionato de estradiol na indução da ovulação de búfalas criadas em várzea da região de Itacoatiara, Amazonas]

This study aimed to determine the efficiency of estradiol cypionate (EC) as an ovulation inducer in a Timed Artificial Insemination protocol. 69 buffalo cows received an intravaginal progesterone device and 2mg of estradiol benzoate (EB) at D0. On D9, the intravaginal device was removed and 0.53mg of prostaglandin (PGF2α) and 400UI of equine chorionic gonadotrophin (eCG) were applied. The cows were distributed into two groups: the first group received 1mg of EC (ECG) in D9, and the second group received 1mg of EB (EBG) in D10. Inseminations occurred on D11. Ovarian activity and pregnancy diagnosis were analyzed by ultrasonography. There was no difference (P>0.05) in follicular diameter (9.6 ± 0.89mm vs. 10.7 ± 1.12mm; P=0.06), in ovulation rate (90.9% vs. 90.9%; P=1) and pregnancy rate (58.8% vs. 62.9%; P=0.79), however, buffalo cows from the ECG treatment have less time between P4 removal and ovulation when compared to EBG buffalos (37.4h vs. 52.8h; P=0.001), respectively. Thus, it was concluded that the implantation of TAI in the floodplain of Amazonas is feasible and the use of EC results in successful rates, similar to EB.(AU)

O objetivo deste trabalho foi determinar a eficiência do cipionato de estradiol (CE) como indutor de ovulação em um protocolo de inseminação artificial de tempo fixo. Para isso, 69 búfalas receberam no D0 um dispositivo intravaginal de progesterona e 2mg de benzoato de estradiol (BE). No D9, o dispositivo intravaginal foi removido e foram aplicados 0,53mg de prostaglandina (PGF2α) e 400UI de gonadotrofina coriônica equina (eCG), para, então, os animais serem divididos em dois grupos: um deles (GCE) recebeu 1mg de CE no D9, e o outro (GBE) recebeu 1mg de BE 24h após. As inseminações ocorreram no D11. A atividade ovariana e o diagnóstico de prenhez foram avaliados por ultrassonografia. Não houve diferença (P>0,05) no diâmetro folicular (9,6 ± 0,89mm vs. 10,7 ± 1,12mm; P=0,06), na taxa de ovulação (90,9% vs. 90,9%; P=1) e na taxa de prenhez (58,8% vs. 62,9%; P=0,79), no entanto búfalas do tratamento GCE apresentaram menor tempo entre a remoção da P4 e a ovulação, quando comparadas com as búfalas do GBE (37,4h vs. 52,8h; P=0,001), respectivamente. A implantação da IATF nas várzeas do Amazonas é viável e a utilização do CE resulta em taxas de sucesso similares ao BE.(AU)

Deficiencia de lipasa ácida lisosomal, una patología infrecuente.

Lysosomal acid lipase deficiency is a genetic disease with a low prevalence and high morbidity and mortality in children and adults. It is characterized by an alteration of lipid metabolism, which generates cholesterol and triglyceride esters deposits in the body. Its clinical presentation depends on enzymatic activity. This condition should be suspected in patients with lipid or liver alterations after ruling out other diagnoses. Currently, there is the option of using a recombinant enzyme, which can improve lipid and liver parameters, as well as disease progression. Establishing a timely diagnosis in order to initiate specific treatment early is imperative for the prevention of morbidity and mortality. The purpose of this work is to perform a review of the literature about lysosomal acid lipase deficiency and to guide about its pathophysiology, clinical manifestations, diagnosis and treatment.

El déficit de lipasa ácida lisosomal es una enfermedad genética poco prevalente, con alta morbimortalidad en niños y adultos. Se caracteriza por alteración del metabolismo lipídico que genera depósitos de ésteres de colesterol y triglicéridos en el organismo. La presentación clínica depende de la actividad enzimática. Se debe sospechar en pacientes con alteraciones lipídicas o alteraciones hepáticas después de descartar otros diagnósticos. Actualmente existe la opción de utilizar enzima recombinante, la cual puede mejorar los parámetros lipídicos y hepáticos, así como detener la progresión de la enfermedad. Es imperioso realizar el diagnóstico oportuno para iniciar de forma temprana el tratamiento específico, con el fin de prevenir la morbimortalidad. Se llevó a cabo revisión de la literatura en torno del déficit de lipasa ácida lisosomal, para orientar acerca de su fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento.

Deficiencia de lipasa ácida lisosomal, una patología infrecuente / Lysosomal acid lipase deficiency, a rare pathology

Resumen El déficit de lipasa ácida lisosomal es una enfermedad genética poco prevalente, con alta morbimortalidad en niños y adultos. Se caracteriza por alteración del metabolismo lipídico que genera depósitos de ésteres de colesterol y triglicéridos en el organismo. La presentación clínica depende de la actividad enzimática. Se debe sospechar en pacientes con alteraciones lipídicas o alteraciones hepáticas después de descartar otros diagnósticos. Actualmente existe la opción de utilizar enzima recombinante, la cual puede mejorar los parámetros lipídicos y hepáticos, así como detener la progresión de la enfermedad. Es imperioso realizar el diagnóstico oportuno para iniciar de forma temprana el tratamiento específico, con el fin de prevenir la morbimortalidad. Se llevó a cabo revisión de la literatura en torno del déficit de lipasa ácida lisosomal, para orientar acerca de su fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento.

Abstract Lysosomal acid lipase deficiency is a genetic disease with a low prevalence and high morbidity and mortality in children and adults. It is characterized by an alteration of lipid metabolism, which generates cholesterol and triglyceride esters deposits in the body. Its clinical presentation depends on enzymatic activity. This condition should be suspected in patients with lipid or liver alterations after ruling out other diagnoses. Currently, there is the option of using a recombinant enzyme, which can improve lipid and liver parameters, as well as disease progression. Establishing a timely diagnosis in order to initiate specific treatment early is imperative for the prevention of morbidity and mortality. The purpose of this work is to perform a review of the literature about lysosomal acid lipase deficiency and to guide about its pathophysiology, clinical manifestations, diagnosis and treatment.

[Synthesis and regulation of flavor compounds derived from brewing yeast: Esters]. / Síntesis y regulación de compuestos del aroma y el sabor derivados de la levadura en la cerveza: ésteres.

During brewing process yeast produce more than 500 chemical compounds that can negatively and positively impact beer at the organoleptic level. In recent years, and particularly thanks to the advancement of molecular biology and genomics, there has been considerable progress in our understanding about the molecular and cellular basis of the synthesis and regulation of many of these flavor compounds. This article focuses on esters, responsible for the floral and fruity beer flavor. Its formation depends on various enzymes and factors such as the concentration of wort nutrients, the amount of dissolved oxygen and carbon dioxide, fermentation temperature and mainly the genetics of the yeast used. We provide information about how the esters originate and how is the impact of different fermentative parameters on the final concentrations of these compounds and the quality of the end product.

Association of a cholesteryl ester transfer protein variant (rs1800777) with fat mass, HDL cholesterol levels, and metabolic syndrome.

BACKGROUND: There is little evidence of the association between CETP SNPs and obesity and/or related metabolic parameters. OBJECTIVE: To analyze the association of the polymorphism rs1800777 of the CETP gene with anthropometric parameters, lipid profile, metabolic syndrome and its components, and adipokine levels in obese subjects without type 2 diabetes mellitus or hypertension. DESIGN: A population of 1005 obese subjects was analyzed. Electrical bioimpedance was performed, and blood pressure, presence of metabolic syndrome, dietary intake, physical activity, and biochemical tests were recorded. RESULTS: Nine hundred and sixty eight patients (96.3%) had the GG genotype, 37 patients the GA genotype (3.7%) (no AA genotype was detected). Fat mass (delta: 4.4±1.1kg; p=0.04), waist circumference (delta: 5.6±2.1cm; p=0.02), and waist to hip ratio (delta: 0.04±0.01cm; p=0.01) were higher in A allele carriers than in non-A allele carriers. HDL cholesterol levels were lower in A allele carriers than in non-A allele carriers (delta: 4.2±1.0mg/dL; p=0.04). In the logistic regression analysis, the GA genotype was associated to an increased risk of central obesity (OR 7.55, 95% CI 1.10-55.70, p=0.02) and low HDL cholesterol levels (OR 2.46, 95% CI 1.23-4.91, p=0.014). CONCLUSION: The CETP variant at position +82 is associated to lower HDL cholesterol levels, increased fat mass, and central obesity in obese subjects. These results may suggest a potential role of this variant gene in pathophysiology of adipose tissue.

Ensayo de migración global en empaques para alimentos: evaluación de patrones internos alternativos / Overall migration test in food packaging: Evaluation of alternative internal standards / Ensaio de migração global em embalagens de alimentos: avaliação de padrões internos alternativos

Resumen En el ensayo de migración global para empaques plásticos destinados a alimentos grasos se emplea triheptadecanoato de glicerilo (GTM) como patrón interno para la cuantificación de los ésteres metílicos de ácidos grasos (FAMEs) por cromatografía de gases. En este trabajo se evaluaron 3-fenil propanoato de etilo (EFP) y ácido tetradecanóico (AM) como patrones internos alternativos. El uso de AM presentó comportamiento lineal (r > 0,99 y %Sb < 5%), buena precisión intermedia (HORRATr % 0,9) y exactitud (%R % 100,6%). En contraste, la evaluación del EFP, demostró que este no es un patrón interno adecuado para la cuantificación de FAMEs. De otra parte, se evaluó estadísticamente que no hay diferencias significativas en el cálculo de la migración global a partir de FAMEs cuantificados usando como patrón interno GTM o AM, mientras que el uso de EFP sí presenta diferencias significativas.

Abstract In the global migration test for plastic packaging intended for fatty foods, glyceryl triheptadecanoate (GTM) is used as the internal standard for the quantification of fatty acid methyl esters (FAMEs) by gas chromatography. In this work, ethyl 3-phenyl propanoate (EFP) and tetradecanoic acid (AM) were evaluated as alternative internal standards The use of AM presented linear behavior (r > 0.99 and %Sb < 5%), good intermediate precision (HORRATr % 0.9), and accuracy (%R % 100.6%). In contrast, the evaluation of EFP demonstrated that this is not an adequate internal standard for the quantification of FAMEs In addition, it was statistically evaluated that there are no significant differences in the calculation of the global migration from FAMEs quantified using either GTM or AM as internal standards, but the use of EFP presents significant differences.

Resumo No ensaio de migração global para embalagens plásticas destinadas aos alimentos gordurosos, é usado o triheptadecanoato de glicerina (GTM) como padrão interno para a quantificação dos ésteres metílicos de ácidos gordos (FAMEs) mediante cromatografia em fase gasosa. Neste papel foram avaliados 3-fenil propanoato de etilo (EFP) e ácido tetradecanóico (AM) como padrões internos alternativos O (AM) apresentou comportamento linear (r > 0,99 e %Sb < 5%), boa precisão intermédia (HORRATr % 0,9) e precisão (%R % 100,6%). Em contraste, a avaliação do (EFP), mostrou que este não é um padrão interno adequado para a quantificação de FAMEs Por outro lado, uma avaliação estatística indicou que não há diferenças significativas no cálculo da migração global de FAMEs quantificadas utilizando como padrão interno GTM ou AM, em contrapartida o uso do EFP apresenta diferenças significativas.

Traditional uses and seed chemical composition of Jatropha spp. (Euphorbiaceae) in Tehuacán-Cuicatlán, México / Usos tradicionales y composición química de la semilla de Jatropha spp. (Euphorbiaceae) en Tehuacán-Cuicatlán, México

Abstract The Tehuacán-Cuicatlán Biosphere Reserve in México holds genetic richness and endemism for the genus Jatropha, but the specific use of the plants and the seed chemical profiles are still unknown. We recorded the traditional forms of use of Jatropha species, and analyzed the chemical composition of Jatropha spp. seeds. For this, a semi-structured survey was conducted in 15 towns, and 20 interviews were applied in each one between May and August 2012 to estimate the Significant Use Level and Relative Use Value per species. Besides, seeds from J. neopauciflora, J. rufescens, and J. rzedowskii were collected between August and October 2013, and to seed flour samples we determined total lipids by the Soxhlet method, crude protein by the Kjendahl method, and ashes according to AOAC methods; fatty acid profile and phorbol esters were determined by gas chromatography and by HPLC, respectively. The species J. neopauciflora, J. oaxacana, J. rufescens, J. ciliata, and J. rzedowskii, are used as traditional medicine, food, and ornaments, except for J. ciliata, for which none use was recorded. The Significant Use Level as food was found not significant, but for medicinal purposes, J. neopauciflora obtained the highest Relative Use Value (9.0 %). The latex is used to treat 13 disorders, including dental problems and oral diseases with a Significant Use Level of 32.9 %; it is also used as a hemostatic. The protein content among species varied from 23.37 to 26.06 %, and total lipids from 34.79 to 36.60 %. The principal unsaturated fatty acids were oleic (25.08 to 30.09 %) and linoleic (44.55 to 48.46 %), and the saturated fatty acids were palmitic (10.11 to 16.50 %) and stearic (9.47 to 11.15 %). Phorbol esters, the main cause of seed's toxicity, were absent in J. neopauciflora, J. rufescens, and J. rzedowskii. In conclusion, the Significant Use Level of Jatropha species studied was low, with little cultural acceptance and sporadic utilization. The Relative Use Value was important for medicinal purposes, especially for J. neopauciflora. The dehulled seeds of J. neopauciflora, J. rufescens, and J. rzedowskii are potentially useful as food, having high protein contents, and unsaturated oleic and linoleic fatty acids. With this study we report three non-toxic Jatropha species and recommend to scientifically validate the antimycotic use of J. neopauciflora latex. Rev. Biol. Trop. 66(1): 266-279. Epub 2018 March 01.

Resumen La Reserva de la Biosfera Tehuacán-Cuicatlán, México contiene riqueza genética y endemismo para el género Jatropha, pero se desconoce el uso específico de las plantas y la composición química de la semilla. Documentamos las formas tradicionales de uso de las especies de Jatropha y, analizamos la composición química de las semillas de las especies de Jatropha. En 15 comunidades se aplicaron 20 entrevistas semiestructuradas entre mayo y agosto de 2012 para estimar el Nivel de Uso Significativo y el Valor de Uso Relativo por especie. Se colectó semilla solo de J. neopauciflora, J. rufescens, y J. rzedowskii entre agosto y octubre de 2013 para determinar mediante los métodos de la AOAC, el contenido total de lípidos en una muestra de 3 g de harina mediante el método de Soxhlet, proteína cruda en una muestra de harina de 0.4 g por el método Kjendahl y ceniza en una muestra de 5 g de harina. El perfil de ácidos grasos se determinó por cromatografía de gases y el contenido de ésteres de forbol mediante HPLC. Las especies registradas fueron J. neopauciflora, J. oaxacana, J. rufescens, J. rzedowskii y J. ciliata, que se usan en medicina tradicional, alimento y como ornamental, excepto J. ciliata, para la cual no se reportó ningún uso. El Nivel de Uso Significativo como alimento no fue importante, pero para propósitos medicinales J. neopauciflora tuvo el mayor Valor de Uso Relativo (9.0 %). El látex es usado para tratar 13 trastornos, incluyendo problemas dentales y enfermedades bucales con un Nivel Significativo de Uso de 32.9 %; y también es usada como hemostático. El contenido de proteína entre especies varió de 23.37 a 26.06 % y los lípidos totales variaron de 34.79 a 36.60 %. Los principales ácidos grasos insaturados fueron oleico (25.08 a 30.09 %) y linoleico (44.55 a 48.46 %); los ácidos grasos saturados fueron palmítico (10.11 a 16.50 %) y esteárico (9.47 a 11.15 %). No se detectó la presencia de ésteres de forbol (la causa principal de la toxicidad de la semilla) en J. neopauciflora, J. rufescens, y J. rzedowskii. En conclusión, el Nivel de Uso Significativo de las especies de Jatropha fue bajo, con poca aceptación cultural y utilización esporádica. El Valor de Uso Relativo fue importante para propósitos medicinales, especialmente para J. neopauciflora. Las semillas sin testa de J. neopauciflora, J. rufescens, y J. rzedowskii son potencialmente útiles como alimento por su alto contenido de proteínas, ácidos grasos insaturados oleico y linoleico. Se identificaron tres especies no toxicas de Jatropha. Se recomienda validar científicamente el uso antimicótico del látex de J. neopauciflora.

Mexican consensus on lysosomal acid lipase deficiency diagnosis. / Consenso mexicano sobre el diagnóstico de la deficiencia de lipasa ácida lisosomal.

INTRODUCTION: Lysosomal acid lipase deficiency (LAL-D) causes progressive cholesteryl ester and triglyceride accumulation in the lysosomes of hepatocytes and monocyte-macrophage system cells, resulting in a systemic disease with various manifestations that may go unnoticed. It is indispensable to recognize the deficiency, which can present in patients at any age, so that specific treatment can be given. The aim of the present review was to offer a guide for physicians in understanding the fundamental diagnostic aspects of LAL-D, to successfully aid in its identification. METHODS: The review was designed by a group of Mexican experts and is presented as an orienting algorithm for the pediatrician, internist, gastroenterologist, endocrinologist, geneticist, pathologist, radiologist, and other specialists that could come across this disease in their patients. An up-to-date review of the literature in relation to the clinical manifestations of LAL-D and its diagnosis was performed. The statements were formulated based on said review and were then voted upon. The structured quantitative method employed for reaching consensus was the nominal group technique. RESULTS: A practical algorithm of the diagnostic process in LAL-D patients was proposed, based on clinical and laboratory data indicative of the disease and in accordance with the consensus established for each recommendation. CONCLUSION: The algorithm provides a sequence of clinical actions from different studies for optimizing the diagnostic process of patients suspected of having LAL-D.

Synthetic acylsugars and their effects on the control of arthropod pests / Acilaçúcares sintéticos e seu efeito no controle de artrópodes-praga

ABSTRACT One of the main problems facing agriculture is the loss of production as a result of the attack of agricultural pests. Alternative ways to work around this problem are being sought. There are substances called acylsugars that are naturally produced by the wild tomato species S. pennellii and affect arthropod pests. The objectives of this work were to synthesize two acylsugars and assess the biological effect of these on the arthropod pests Bemissia tabaci and Tetranycus urticae. The syntheses were performed via the reactions of glucose and sucrose (saccharose) with acetic anhydride using sodium acetate as the catalyst. The products of these reactions were sucrose octa-acetate and glucose penta-acetate, the structures of which were confirmed by spectroscopic techniques. In a resistance test against the mite, a linear correlation between the concentration of the synthesized substances, and the dislocation of the mite was obtained. A delay in the hatching of the arthropod eggs was observed, causing a mortality rate of approximately 95% in the 1st instar larvae of mites that was confirmed in adults. In the biological tests with Bemisia tabaci, there was a low rate of hatching and emergence, and the effect on the nymphs was the deformation of the emergent adults.

RESUMO Um dos grandes problemas que a agricultura enfrenta é a perda de produção causada pelo ataque de pragas agrícolas. Assim, buscam-se maneiras alternativas de contornar esse problema. Dentre esses, encontram-se substâncias, denominadas de acilaçúcars, que são produzidas naturalmente por espécies selvagens do tomate S. pennellii e que apresentam efeito sobre artrópodes-praga. Os objetivos desse trabalho foram sintetizar dois compostos de acilaçúcares e avaliar o efeito biológico destas sobre os artrópodes-praga Bemissia tabaci e Tetranycus urticae. A síntese foi feita via as reações de glicose e sacarose com anidrido acético, utilizando acetato de sódio como catalisador. Os produtos dessas reações foram o octa-acetato de sacarose e o penta-acetato de glicose, cujas estruturas foram confirmadas por técnicas espectroscópicas. No teste de resistência do ácaro, foi possível obter um ajuste linear entre a concentração das substâncias sintetizadas e o deslocamento do ácaro. Ambas as substâncias obtidas apresentaram um atraso na eclosão dos ovos do artrópode, ocasionando uma mortalidade de aproximadamente 95% em ácaros de 1º ínstar que foram confirmadas em adultos. Nos testes biológicos com Bemisia tabaci, verificou-se uma baixa taxa de eclosão e emergência, sendo que o efeito sobre as ninfas foi a má formação para adultos emergidos.

Update on lysosomal acid lipase deficiency: Diagnosis, treatment and patient management. / Actualización en deficiencia de lipasa ácida lisosomal: diagnóstico, tratamiento y seguimiento de los pacientes.

Lysosomal acid lipase deficiency (LALD) is an ultra-rare disease caused by a congenital disorder of the lipid metabolism, characterized by the deposition of cholesterol esters and triglycerides in the organism. In patients with no enzyme function, the disease develops during the perinatal period and is invariably associated with death during the first year of life. In all other cases, the phenotype is heterogeneous, although most patients develop chronic liver diseases and may also develop an early cardiovascular disease. Treatment for LALD has classically included the use of supportive measures that do not prevent the progression of the disease. In 2015, regulatory agencies approved the use of a human recombinant LAL for the treatment of LALD. This long-term enzyme replacement therapy has been associated with significant improvements in the hepatic and lipid profiles of patients with LALD, increasing survival rates in infants with a rapidly progressive disease. Both the severity of LALD and the availability of a specific treatment highlight the need to identify these patients in clinical settings, although its low prevalence and the existing clinical overlap with other more frequent pathologies limit its diagnosis. In this paper we set out practical recommendations to identify and monitor patients with LALD, including a diagnostic algorithm, along with an updated treatment.

Busca por oxidantes quirais para a transformação enantiosseletiva de compostos orgânicos de boro / Search for chiral oxidants for the enantioselective transformation of organic boron compounds

Neste trabalho, avaliou-se o potencial do uso de oxidantes quirais em oxidações enantiosseletivas de compostos orgânicos de boro. É de conhecimento geral que compostos orgânicos de boro, especialmente ésteres e ácidos borônicos são facilmente oxidados por hidroperóxidos em meio básico. No entanto, são escassos na literatura exemplos destas reações de modo enantiosseletivo. A fim de realizar as reações mencionadas, sintetizou-se os hidroperóxidos quirais TADOOH ({(4R,5R)-5-[(hidroperoxidifenil)metil]-2,2-dimetil-1,3-dioxolan-4il}difenilmetanol) e o hidroperóxido quiral derivado de carboidrato, 2,3-dideoxi1-O-oxidanil-4,6-di-O-pivaloil-α-D-eritro-hex-2-enopiranose (di-O-PivOOH). Estes compostos apresentaram resultados interessantes na literatura em oxidações enantiosseletiva de sulfetos orgânicos, em epoxidações de alcenos e em oxidações de Baeyer-Villiger. Inicialmente o potencial oxidativo de ambos hidroperóxidos, bem como a seletividade destes, foi avaliado frente a diversos ésteres borônicos, sendo que somente o TADOOH apresentou resultados promissores. (Ver esquema no PDF) Observou-se uma melhor seletividade do TADOOH frente a ésteres borônicos que possuíam grupos carbonílicos em sua estrutura. Ao submeter o ß-boronil-éster, 3-fenil-3-(4,4,5,5-tetrametil-1,3,2-dioxaborolan-2-il)propanoato de etila, à oxidação com o TADOOH em THF utilizando NaOH como base, a -30°C por 1 hora, obteve-se o respectivo álcool com 40% de e.e. Cálculos de DFT para o estado de transição na oxidação dos ésteres borônicos com o TADOOH foram realizados em colaboração com o grupo do Prof. Dr. Ataualpa Albert Carmo Braga. Estes cálculos demonstraram que o estado de transição é estabilizado por uma ligação de hidrogênio não clássica entre o oxigênio da carbonila e umas das ligações C-H dos grupos fenila do TADOOH. Além dos estudos relatados, a reconhecida metodologia de Sharpless na epoxidação assimétrica de alcoóis alílicos foi adaptada para a oxidação enantiosseletiva de ésteres borônicos. Ao trocar o ligante derivado de éster tártarico, normalmente utilizado nas epoxidações de Sharpless, por (-)-efedrina observou-se uma moderada seletividade deste sistema frente ao pinacol l-fenietilboronato. Investigações mais detalhadas demonstraram que a presença do Ti(IV) não era necessária, sendo que a (-)efedrina era a responsável pela ativação e indução quiral nesta reação.

In this work, it was investigated the potential use of chiral oxidants in organic boron compound oxidation. It is known in the literature, that organic boron compounds can be easily oxidized by hydroperoxides. However, an enantioselective approach in literature is scarce. In order to perform these reactions, hydroperoxide TADOOH ({(4R,5R)-5[(hydroperoxydiphenyl)methyl]-2,2-dimethyl-l,3-dioxolan-4-yl}diphenylmethanol) and carbohydrate derived hydroperoxide, 2,3-dideoxy-1-O-oxidanyl-4,6-di-O-pivaloyl-α-D-erythro-hex-2-enopyranose (di-O-PivOOH), have been synthesized. These compounds showed interesting results in several enantioselective oxidations, as like, organic sulfides oxidation, alkenes epoxidation and Baeyer-Villiger oxidations. The oxidative potential of both hydroperoxides, as well as their selectivity, were evaluated against several boronic esters. Only TADOOH has shown promissing results for further studies. (See Scheme on PDF). Boronic esters containing a carbonyl moiety showed better selectivities with TADOOH, for example, the reaction of ß-boronyl-ester, ethyl 3-phenyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)propanoate, gave the correponding alcohol with 40% e.e. DFT calculations for the transition state in the oxidation of the boronic esters with TADOOH were carried out in collaboration with the group of Prof. Dr. Ataualpa Albert Carmo Braga. These calculations have shown that the transition state is stabilized by a non-classical hydrogen bond between the carbonyl oxygen and one of the C-H bonds of the TADOOH phenyl groups. In addition to the studies, the well-known Sharpless protocol for asymmetric epoxidation of allylic alcohols was adapted in the enantioselective oxidation of boronic esters. By replacing the tartaric ester-derived, commonly used in the Sharpless experiments, for (-)-ephedrine moderate selectivity was observed with pinacol 1-phenylethyl boronate. Further investigations showed that the presence of Ti (IV) was not necessary, and (-)-ephedrine was responsible for the activation and chiral induction in this reaction.

Guía colombiana para el diagnóstico de la deficiencia de lipasa ácida / Colombian Guidelines for Diagnosis of Lipase Acid Deficiency

Resumen Introducción: la deficiencia de lipasa ácida lisosomal (LAL-D) es una entidad de herencia autosómica recesiva que lleva a la acumulación de esteres de colesterol y triglicéridos en el hígado, bazo y otros órganos. La edad de inicio y la tasa de progresión son muy variables, lo que posiblemente sea explicado por las mutaciones presentes en el gen LIPA. Las manifestaciones clínicas son las mismas que para otras patologías hepáticas, cardiovasculares y metabólicas, lo que hace difícil reconocerla en la práctica clínica. Objetivo: proveer una guía que permita a los clínicos reconocer los principales grupos de riesgo en los cuales se debe sospechar de LAL-D y mejorar su diagnóstico. Metodología: este documento se diseñó como un consenso de expertos en el cual participaron médicos especialistas en gastroenterología, hepatología, endocrinología, genética, patología y pediatría. Se realizó una revisión de la literatura acerca de las manifestaciones clínicas y de las herramientas para el diagnóstico de LAL-D y se siguió la metodología de técnica de grupo nominal. Resultados: se generaron algoritmos diagnósticos por consenso para cada uno de los grupos de riesgo, que facilitaran la sospecha y el diagnóstico de LAL-D. Conclusiones: esta guía propone algoritmos para el diagnóstico de LAL-D con base en el consenso clínico, que buscan optimizar la ruta diagnóstica en los pacientes con dicha patología.

Abstract Introduction: Lysosomal acid lipase deficiency (LAL-D) is an inherited autosomal recessive entity that leads to the accumulation of cholesterol and triglyceride esters in the liver, spleen and other organs. The age of onset and rate of progression vary greatly, possibly explained by mutations of the LIPA gene. Clinical manifestations are the same as those of other hepatic, cardiovascular and metabolic pathologies which makes it difficult to recognize in clinical practice. Objective: The objectives of these guidelines is to help clinicians recognize the major groups at risk for LAL-D and to improve its diagnosis. Methodology: This document was designed as a consensus of experts in gastroenterology, hepatology, endocrinology, genetics, pathology and pediatrics. A review of the literature regarding clinical manifestations and tools for diagnosis of LAL-D was conducted and the nominal group technique was followed. Results: Diagnostic algorithms which facilitate suspicion and diagnosis of LAL-D were generated by consensus for each of the risk groups. Conclusions: This guide proposes algorithms for the diagnosis of LAL-D based on clinical consensus. The algorithms seek to optimize diagnosis for patients with this pathology.

Producción de ésteres volátiles a través de tecnología de fermentaciones utilizando residuos cítricos / Volatile ester production using citrus waste through fermentation technology

La acumulación de residuos generados por las industrias procesadoras de alimentos, entre ellos, los residuos cítricos producidos en el procesamiento de jugos, constituyen una problemática desfavorable para el medio ambiente. En diversos países incluyendo Bolivia no existen gestiones que se apliquen al manejo y aprovechamiento de estos residuos, los cuales representan aproximadamente más del 50 % del total de la fruta, por ello es necesaria una gestión integrada de estos residuos de acuerdo al concepto de reducir, reutilizar y reciclar. En el Área de Biotecnología Microbiana del Instituto de Investigaciones Fármaco Bioquímicas, se estudia una alternativa de manejo y aprovechamiento de estos residuos cítricos, investigando la utilización de los mismos como materia prima para la producción de ésteres volátiles que tienen propiedades biosaborizantes. La conversión de residuos cítricos a biosabores se lleva a cabo mediante procesos biotecnológicos de fermentación de azúcares que involucran el uso de microorganismos como levaduras. Para ello, se plantea el estudio del comportamiento cinético de Cándida maltosa asociado a su capacidad de producir ésteres volátiles, considerando que esta levadura es capaz de formar biopelículas como forma de protección ante compuestos inhibitorios propios de la materia prima.

The accumulation of wastes from food processing industries, among them the citrus residues from the juice-processing industry becomes an issue due to its unfavorable impact for the environment. Several countries including Bolivia do not have alternatives for waste management. The citrus waste accounts 50% of the fruit. Therefore,an integrated procedure under the concept to reduce-reuse-recycling is needed.An alternative for management and reuse of citric waste is planned at the Microbial Biotechnology Area of Instituto de Investigaciones Fármaco Bioquímicas. Moreover, the utilization of citrus waste as feedstock for the production of volatile esters, with flavoring properties, is being researched.The conversion of citrus waste to bioflavors can be carried out by sugars-fermenting yeast through biotechnology. Therefore, studies involving the kinetic behaviour of Candida maltosa associated to volatile ester production are planned. This yeast is able to form biofilm as a protection skill against inhibitory compounds from the feedstock.

Emulsificantes: atuação como modificadores do processo de cristalização de gorduras / Emulsifiers: acting as modifiers of the crystallization behaviour of fats

Os emulsificantes são aditivos empregados com diversas finalidades na produção dos alimentos industrializados, dentre elas para melhorar a textura, o volume, a aeração e a homogeneidade dos produtos. Estudos indicam mais uma função para estes compostos que atuam usualmente estabilizando emulsões, como modificadores do processo de cristalização de óleos e gorduras. Produtos como chocolates, margarinas e sorvetes são elaborados com base nos compostos gordurosos que, ao atingirem a condição de super-resfriamento ou supersaturação, formam cristais e, posteriormente, uma rede cristalina tridimensional, responsável pelos atributos sensoriais dos produtos. Os emulsificantes podem interferir no tempo de indução, na velocidade de formação dos cristais de gordura, além de modificar a morfologia e o hábito cristalino desses cristais, retardando as transições polimórficas indesejáveis e afetando diretamente a qualidade dos produtos. Esta revisão abordou os diferentes efeitos de emulsificantes utilizados em alimentos na cristalização de matérias-primas gordurosas.

The emulsifiers are additives used for many purposes in the production of foods, among them to improve texture, volume, aeration and homogeneity of the products. Most studies indicate a new role for this compound that acts usually stabilizing emulsions, as modifier of the crystallization of oils and fats. Products such as chocolate, margarine and ice cream which are made of fats, upon reaching the condition of supercooling or supersaturation, form crystals and then a three-dimensional crystal lattice responsible for sensory attributes of products. The emulsifiers can alter induction time, the rate of formation of fat crystals and modify the morphology and crystal habit of these crystals, retarding undesired polymorphic transitions and affecting quality of products. This review evaluated the effects of different food emulsifiers on the crystallization of fats.

[New approaches for the treatment of dyslipidemia]. / Nuevas pautas en el tratamiento de las dislipidemias.

Reduction in the risk of cardiovascular complications through modification of lipids is currently focused on lowering low density lipoproteins-cholesterol, with statins being the preferred drugs. New agents, under research, such as antibodies neutralizing PCSK9, will have a special place for the management of patients with intolerance to statins of severe dyslipemias. Drugs used to modify the concentration of high density lipoproteins-cholesterol and triglycerides have not been accompanied by the expected reductions in the rate of cardiovascular complications.

Effects of Euphorbia milii latex on mitogen-induced lymphocyte proliferation / Efeito do latex de Euphorbia milii sobre a proliferação de linfócitos induzida por mitogénio

The crude latex of "Crown-of-Thorns" (Euphorbia milii var hislopii, syn E.splendens) is a potent plant molluscicide. For this reason, toxicological studies have been performed to evaluate the health risks posed by its use in schistosomiasis control programs. The present study is part of a more comprehensive immunotoxicological evaluation of this molluscicide. Here, we investigated the effects of E. milii latex on the proliferation of human lymphocytes in vitro. Lyophilized latex of E. milii (0, 0.5, 5, 25 and 50 µg/ml) was incubated with whole blood in the presence of proliferation stimulators, i.e. lectins (phytohemagglutinin, concanavalin A and pokeweed mitogen), as well as with human monoclonal antibody against CD3 and tetanus toxoid. Cell proliferation was measured by ³H-thymidine incorporation, and the effects of latex on mitogen-induced cell proliferation were compared to the effects of 10 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA). Results showed that mitogen-induced cell proliferation was markedly enhanced by E. milii latex. This synergistic effect of latex on mitogen-induced lymphocyte proliferation may be due to the presence of TPA-like phorbol esters and/or to mitogenic plant lectins.

O látexbrutoda "Coroa de Cristo" (Euphorbia miliivarhislopii, syn E.splendens) é um potente moluscicidavegetal. Neste sentido, são necessários estudos toxicológicosque visemavaliar possíveis riscos à saúdeassociados ao uso em larga escala desta espécie em áreas endêmicas para esquistossomose. O presente estudo é parte deuma avaliação mais abrangentesobre o potencial tóxico destemoluscicida. Foram investigados in vitro osefeitos dolátex da E.miliisobre a proliferação delinfócitoshumanos. O látexliofilizado (0; 0,5;5;25 e 50 µg/ml)foi incubado comsangue totalna presençade agentes mitogênicos, tais como lectinas(fitohemaglutinina, concanavalina Ae pokeweed), anticorpomonoclonalhumano anti-CD3etoxóide tetânico. A proliferação celularfoi quantificada atravésincorporaçãode ³H-timidina eos efeitos do látexnaproliferação celular induzida por agentes mitogênicosforam comparados comos efeitos de10 ng/mlde12-O-tetradecanoilforbol-13-acetato (TPA). Os resultados demonstram quea proliferação celular induzida poragentes mitogênicosfoimarcadamenteaumentada na presença do látex daE.milii.Oefeito sinérgico observado pode ser devidoà presença deésteres de forbol, como o TPA, e/oude lectinas com ação mitogênica presentes nesta espécie vegetal.