In the present work five acetylene derivatives (1-5), including three unknowns (1, 3 and 4), were isolated from seeds of Porcelia macrocarpa (Annonaceae). The structures of isolated compounds were determined as docos-13-yn-21-enoic acid (1), 3-hydroxy-4-methylene-2-(eicos-11’-yn-19’-enyl)but-2-enolide (2), 3-hydroxy-4-methylene-2-(octadec-9’-yn-17’-enyl)but-2-enolide (3), 3-hydroxy-4-methylene-2-(hexadec-7’-yn-15’-enyl)but-2-enolide (4), and (2S,3R,4R)-3-hydroxy-4-methyl-2-(eicos-11’-yn-19’-enyl)butanolide (5) by analysis of nuclear magnetic resonance (NMR) and electrospray ionization high-resolution mass spectrometry (ESI-HRMS) data. Moreover, all isolated compounds demonstrated selectivity towards intracellular amastigotes of Leishmania (L.) infantum, especially 2-4 with 50% inhibitory concentration (IC50) values of 9.2, 10.4 and 11.0 µM, respectively, indicating superior activity of that determined to positive control miltefosine (IC50 of 17.8 µM). Furthermore, these compounds showed higher selectivity index (SI) in comparison with miltefosine. Since related acetylene fatty acid 1 displayed reduced antiparasitic potential (IC50 of 48.5 µM), the obtained results suggested that the γ-lactone plays an important role in the antileishmanial activity. However, 2-4 exhibited cytotoxicity to mammalian NCTC cells (CC50 ca. 80 µM), which could be a result of the presence of a conjugated carbonyl system in the lactone ring, since 5, the only acetogenin that presents the saturated ring, lacked mammalian cytotoxicity (CC50 > 200 µM).

RESUMO Embora o diagnóstico da EM tenha se modificado na última década, ainda tem como requisito básico a demonstração da disseminação no tempo e no espaço, através do quadro clínico e do exame de ressonância magnética. A síntese intratecal de imunoglobulina pode ser um marcador inespecífico e não há biomarcadores plasmáticos que sejam úteis no diagnóstico da EM, impondo desafios à sua detecção precoce. Métodos Realizamos uma análise lipidômica preliminar por espectrometria de massas, não direcionada, qualitativa, comparando amostras de LCR e plasma de pacientes com EM, outras doenças neurológicas inflamatórias e hipertensão intracraniana idiopática (HII). Resultados A identificação lipídica revelou que os ácidos graxos e esfingolipídios foram as classes mais abundantes de lipídios no LCR e que glicerolipídios e ácidos graxos foram a principal classe de lipídios no plasma de pacientes com EM. A AUC foi de 0,995 (0,912–1) e 0,78 (0,583–0,917), respectivamente. O teste de permutação indicou que essa combinação de íons foi útil para distinguir a EM de outras doenças inflamatórias (p < 0,001 e 0,055, respectivamente). Conclusão Este estudo sugere que o líquido cefalorraquidiano (LCR) e o plasma de pacientes com EM possuem uma assinatura lipídica única, pode ser útil como um biomarcador diagnóstico.

ABSTRACT The diagnosis of multiple sclerosis (MS) has changed over the last decade, but remains a composite of clinical assessment and magnetic resonance imaging to prove dissemination of lesions in time and space. The intrathecal synthesis of immunoglobulin may be a nonspecific marker and there are no plasma biomarkers that are useful in the diagnosis of MS, presenting additional challenges to their early detection. Methods We performed a preliminary untargeted qualitative lipidomics mass spectrometry analysis, comparing cerebrospinal fluid (CSF) and plasma samples from patients with MS, other inflammatory neurological diseases and idiopathic intracranial hypertension. Results Lipid identification revealed that fatty acids and sphingolipids were the most abundant classes of lipids in the CSF and that glycerolipids and fatty acids were the main class of lipids in the plasma of patients with MS. The area under the curve was 0.995 (0.912–1) and 0.78 (0.583–0.917), respectively. The permutation test indicated that this ion combination was useful for distinguishing MS from other inflammatory diseases (p < 0.001 and 0.055, respectively). Conclusion This study concluded that the CSF and plasma from patients with MS bear a unique lipid signature that can be useful as a diagnostic biomarker.

Cyanobacteria are prokaryotic and photosynthetic organisms, which can produce a wide range of bioactive compounds with different properties; including a variety of toxic compounds, also known as cyanotoxins. In this work, we describe the isolation of seven cyanobacterial strains from two reservoirs in São Paulo State, Brazil. Seven different chemical variants of microcystins (MC-RR, MC-LR, MC-YR, MC-LF, MC-LW, and two demethylated variants, dm-MC-RR and dm-MC-LR) were detected in three of the ten isolated strains. One particular Microcystis aeruginosa strain (LTPNA 02) was chosen to evaluate its growth by cell count, and its toxin production under seven different nutritional regimes. We observed different growth behaviors in the logarithmic growth period for only three experiments (p <0.05). The total growth analysis identified four experiments as different from the control (p < 0.01). Three microcystin variants (MC-RR, MC-LR and MC-YR) were quantified by liquid chromatography-tandem mass spectrometry. At the experimental end, the toxin content was unchanged when comparing cell growth in ASM-1 (N:P = 1), MLA and BG-11 (N:P = 10) medium. In all other experiments, the lowest microcystin production was observed from cells grown in Bold 3N medium during the exponential growth phase. The highest microcystin content was observed in cultures using BG-11(N:P = 100) medium.

JUSTIFICATIVA E OBJETIVOS: Existem várias formulações de propofol para uso clínico à disposição do anestesiologista. O objetivo desse estudo foi analisar as propriedades físico-químicas, o efeito farmacodinâmico e a equivalência farmacêutica e clínica do fármaco referência de propofol e uma formulação similar. MÉTODOS: Dezesseis voluntários participaram desse estudo aleatório, duplamente encoberto e pareado entre as formulações Diprivan® e Propovan®. As formulações foram administradas em regime de infusão alvo-controlada com concentração-alvo de 3,0 µg.mL-1 por 15 minutos. As variáveis estudadas foram a área sob a curva (ASC) do gráfico do índice bispectral (BIS) em relação ao tempo, o BIS mínimo atingido e o tempo para tal e o tempo de recuperação. As duas formulações foram submetidas às análises de tamanho de partículas da emulsão lipídica, potencial de superfície e quantificação de princípio ativo. RESULTADOS: Não houve diferença entre as formulações quando se comparou a ASC, BIS mínimo atingido e o tempo decorrido para tal. O tempo de recuperação com a formulação similar foi menor em relação à referência (oito e 10 min, respectivamente, p = 0,014). O tamanho médio de partículas da emulsão lipídica, potencial de superfície e a quantificação de princípio ativo foram semelhantes nas duas formulações. CONCLUSÃO: Não houve diferença clínica significativa entre o uso de propofol referência Diprivan® e seu similar Propovan® durante a infusão. Entretanto, o tempo de recuperação foi mais prolongado com o fármaco referência. Embora as análises com as duas formulações estudadas mostrarem resultados semelhantes quanto a sua caracterização físico-química, outros estudos devem ser realizados para justificar tal diferença.

BACKGROUND AND OBJECTIVES: There are several formulations of propofol available to the anesthesiologist for clinical use. The aim of this study was to analyze the physicochemical properties, pharmacodynamic effect, and pharmaceutical and clinical equivalence of the reference drug propofol as well as a similar formulation. METHOD: Sixteen volunteers were enrolled in this randomized, double-blind, and paired study of Diprivan® and Propovan® formulations. Formulations were given as target-controlled infusion with target concentration of 3.0 μg.mL-1 for 15 minutes. Variables studied were the area under the curve (AUC) of the bispectral index (BIS) graph regarding time, minimum BIS reached and time to reach it, and recovery time. The two formulations were sent to analysis of particle size of lipid emulsion, surface potential, and active principle quantification. RESULTS: There was no difference between the formulations when comparing AUC, minimum BIS reached and time to reach it. The similar formulation recovery time was lower compared to the reference formulation (eight and 10 min, respectively, p = 0.014). Mean particle size of lipid emulsion, surface potential, and active ingredient quantification were similar for both formulations. CONCLUSION: There was no clinically significant difference between the use of propofol, reference Diprivan®, and the similar Propovan® during infusion. However, the recovery time was longer with the reference drug. Although analysis of both formulations studied show similar results regarding its physicochemical characterization, further studies should be conducted to justify this difference.

JUSTIFICATIVA Y OBJETIVOS: Existen varias formulaciones de propofol para el uso clínico que están disponibles para el anestesiólogo. El objetivo de este estudio, fue analizar las propiedades físico-químicas, el efecto farmacodinámico y la equivalencia farmacéutica y clínica del fármaco referencia de propofol y una formulación similar. MÉTODO: Dieciséis voluntarios participaron en este estudio aleatorio, doble ciego y pareado entre las formulaciones Diprivan® y Propovan®. Las formulaciones fueron administradas en un régimen de infusión objeto-controlada con una concentración objetivo de 3,0 µg.mL-1 durante 15 minutos. Las variables estudiadas fueron el área bajo la curva (ASC) del gráfico del índice bispectral (BIS) con relación al tiempo, el BIS mínimo alcanzado y el tiempo para tal, y el tiempo de recuperación. Las dos formulaciones se sometieron a los análisis de tamaño de partículas de la emulsión lipídica, potencial de superficie y cuantificación del principio activo. RESULTADOS: No hubo diferencia entre las formulaciones cuando se comparó la ASC, el BIS mínimo alcanzado y el tiempo transcurrido para tal. El tiempo de recuperación con la formulación similar fue menor con relación a la referencia (8 y 10 min, respectivamente, p = 0,014). El tamaño promedio de partículas de la emulsión lipídica, potencial de superficie y la cuantificación del principio activo, fueron similares en las dos formulaciones. CONCLUSIONES: No hubo diferencia clínica significativa entre el uso de propofol referencia Diprivan® y su similar Propovan® durante la infusión. Sin embargo, el tiempo de recuperación se extendió más con el fármaco de referencia. Aunque los análisis de las formulaciones estudiadas muestren resultados similares en cuanto a su caracterización físico-química, otros estudios deben ser realizados para justificar tal diferencia.