2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells.

The anticancer potential of 2-amino-1,3,4-thiadiazole compounds has been documented by in vitro and in vivo studies. In our previous research, we described the synthesis as well as the antiproliferative and neuroprotective activities of 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FABT). The aim of the present study was to investigate the molecular mechanisms involved in FABT-induced growth inhibition in A549 lung carcinoma cells. Western blotting analysis revealed that FABT inhibited the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and Real-time PCR analysis showed no changes in the expression of P44ERK1 and CREB1 genes. Furthermore, FABT induced cell cycle arrest in the GO/G1 phase and enhanced p27/Kip1 expression. Our results suggest that FABT acts by inhibiting ERK1/2 pathway and cell cycle progression through G1 into S phase in A549 cells. Further studies are needed to completely explain the molecular mechanisms of anticancer action of this 2-aminothiadiazole derivative.

Transcription factor GATA3 expression is induced by GLS2 overexpression in a glioblastoma cell line but is GLS2-independent in patient-derived glioblastoma.

Phosphate-activated glutaminase (GA), a ubiquitous glutamine-metabolizing enzyme, is encoded by two genes, GLS and GLS2. In mammalian cancers, GLS isoforms are perceived as molecules promoting cell proliferation and invasion, whereas the role of GLS2 isoforms seems to be more complex and cell type-specific. Previous studies have shown abundance of GLS and lack of GLS2 transcripts in T98G human glioblastoma (GBM) cell line and patient-derived GBM. Transfection with GAB sequence, the whole GLS2 cDNA transcript, suppressed malignant phenotype of T98G cells. Microarray analysis revealed upregulation of GATA3, the product of which has been implicated in suppressing growth of some peripheral cancers. In this study we confirmed a significant upregulation of GATA3 expression in the transfected cells both at mRNA and protein level. Considerable expression of GATA3 was also observed in GBM tissues (previously shown as not expressing GLS2), while only traces or no GATA3 was detected in (GLS2-expressing) non-tumorigenic brain samples. In conclusion, while mechanistic relation between GAB and GATA3 expression is evident following in vitro manipulation of GBM cell line, it does not appear to be an intrinsic property of GBM nor non-tumorigenic brain tissue.

[The diffusion and dissolution of metronidazole and doxepin in semisolid pharmaceutical forms through synthetic membranes]. / Estudio de difusión y disolución de metronidazol y doxepina en formas farmacéuticas semisolidas a través de membranas sintéticas.

The dissolution and diffussion methods through homogeneous synthetic membrane were studied in different semisolid topical formulations containing metronidazole and doxepin. The results suggest that the rate of release showed a first order kinetic for one of the formulations and the rate of release described by Higuchi for the others.

[The effect of nitrofurazone and furazolidone on induction of cytochrome P-450 in the CYPIA test]. / Okreslenie wplywu nitrofurazonu i furazolidonu na indukcje cytochromu P-450 w tescie-CYPIA.

The double CYPIA-TEST (cytochrome P-450) induction assay) was used to discriminate between the forms of cytochrome P-450 (the 3-methylcholantrene type (3-MC) or phenobarbital type (PB)) induced by nitrofurans; nitrofurazone and furazolidone. The test consisted of the studies by the technique of Ames of the ability of the S9 preparation obtained from livers of rats induced by nitrofurans to cause the metabolic activation of ethidium bromide (EtBr)--for induction of 3-MC type or cyclophosphamide (CPA) for PB type of cytochrome P-450. The mutagenicity of activated EtBr and CPA was checked with TA98 and TA100 of S. typhimurium respectively. It was found that only furazolidone at cumulative dose 3 x 80 mg/kg of body weight induce the 3-MC-type of cytochrome P-450.

Rifampicina y biodisponibilidad en productos combinados / Rifampicin and bioavailability in combination formulation

La rifampicina (R) es un antibiótico de primera elección en el tratamiento de la tuberculosis (TB) junto a la Isoniazida (H), Pirazinamida (Z) y Etambutol (E). De acuerdo a las últimas estadísticas, la TB aumentó a nivel mundial y entre las causas más citadas figuran: las monoterapias, la aparición de microorganismos resistentes, la carencia de programas efectivos, el incumplimiento en el tratamiento y las dosis erróneas. La Organización Mundial de la Salud (OMS) y la Unión Internacional Contra la Tuberculosis y Enfermedades de Pulmón (IUATLD) declararon a la enfermedad en emergencia mundial y establecieron programas terapéuticos para asegurar el cumplimiento y disminuir los problemas relacionados a la terapia. Sobre esta base, figura en la lista oficial la asociación de los cuatro fármacos de primera línea R, Z, H y E combinados en dosis fijas (FDC) que permiten la administración conjunta de los mismos y, en las dosis correctas. Los productos FDC son recomendados oficialmente por la OMS para el tratamiento de la TB. No obstante existen factores que alteran la biodisponibilidad de la R en estas formulaciones, hecho ampliamente reconocido en publicaciones científicas. El objetivo de este trabajo es estudiar los aspectos más relevantes que alteran la biodisponibilidad de la R en los productos FDC y plantear posibles soluciones al problema

The drug rifampicin (R) is used as a first line antibiotic treatment for tuberculosis (TB), together with Isoniazide (H), Pyrazinamide (Z) and Ethambutol (E). According to recent statistics, there has been an increase in TB on a worldwide scale, with the main causes being: monotherapies, the appearance of resistant microorganisms, the lack of effective preventative programs, non-compliance to treatment and mistaken dosage schedules. The world health organisation (WHO) and the International Union Against Tuberculosis and Lung Diseases(IUTALD) declared a state of emergency with respect to the disease and established programs to increase compliance to therapy and to reduce the incidence of problems arising from such. Along these lines, a list of first line drug therapy treatments were established, which included R, Z, H & E combinations at fixed dosage combinations (FDC), permitting safe combined administrations of the drugs at correct dosage levels. These fixed dose combinations have been officially recommended by the WHO in the treatment of TB. However, as has been widely recognised in numerous scientific publications, in such formulations, there are factors that alter the bioavailability of R. The objective of this work has been to study the most relevant aspects concerning R bioavailability alterations and to consider possible solutions to the problem

Micropartículas de alginatoconteniendo paracetamol / Alginate microparticles containing paracetamol

Micropartículas conteniendo paracetamol (PCT) han sido obtenidas por emulsificación/gelificación interna de una solución de alginato dispersada en un aceite vegetal. La morfología y la distribución de tamaño de partícula fueron determinadas. Se estudió la concentración de ión calcio resultando ser un parámetro crítico en la producción de las micropartículas. Se observó que el incremento en la concentración de calcio produce un aumento en el rendimiento total de micropartículas y en el encapsulación de PCT. La técnica desarrollada permite obtener un sistema con características micrométricas óptimas y una mayor eficacia de encapsulación de PCT (AU)