Flavonoids of Tripodanthus acutifolius inhibit TNF-α production in LPS-activated THP-1 and B16-F10 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: T. acutifolius is an endemic species from South America which has been used in traditional medicine since ancient times due to its biological properties, including its anti-inflammatory effects. AIM OF THE STUDY: The aim of the article is to investigate the inhibitory activity of T. acutifolius over TNF-α production in THP-1 and B16-F10 cells. To achieve this, phytochemical analysis has been used to determine the compounds present in the species with anti-inflammatory effects. MATERIALS AND METHODS: Leaves and stems of T. acutifolius were extracted with n-heptane, dichloromethane, methanol and water. The resulting extracts were analysed in THP-1 and B16-F10 cells by measuring their inhibitory capacity over the production of TNF-α stimulated with LPS. RESULTS: The guided-bioassay led to the isolation of 6,2',4'-trimethoxyflavone (1), 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone (2), (E)-2',4'-dihydroxy-6'-methoxy-chalcone (3) and 5,4'-dihydroxy-6,7,8-trimethoxyflavone (4) from the dichloromethanic extract. Compounds showed an inhibitory activity of TNF-⍺ production in THP-1 cells, with IC50 of 2.38 ±â€¯0.02 µM, 12.36 ±â€¯0.17 µM, 1.12 ±â€¯0.01 µM and 8.09 ±â€¯0.04 µM, respectively. In addition, the compounds showed an inhibitory activity of TNF-⍺ production in B16-F10 cells with IC50 of 1.32 ±â€¯0.03 µM, 5.63 ±â€¯0.09 µM, 0.60 ±â€¯0.02 µM and 3.77 ±â€¯0.15 µM, respectively. CONCLUSIONS: We identified 3 flavones (6,2',4'-trimethoxyflavone, 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone, 5,4'-dihydroxy-6,7,8-trimethoxyflavone) and a chalcone ((E)-2',4'-dihydroxy-6'-methoxy-chalcone) present in the leaves and stems of T. acutifolius. These compounds are an alternative for the treatment of immune-mediated inflammatory disorders, acting as negative modulators over the TNF-α production.

Successful methotrexate treatment of an abdominal pregnancy in the pouch of Douglas.

Abdominal pregnancy is a rare localization of ectopic pregnancy. Early diagnosis and treatment are advised and the choice of treatment is crucial. A successful case of conservative treatment with combined systemic and intra-amniotic methotrexate is presented. This treatment option should be considered in the management of this potentially life-threatening condition.

Uric acid calculi: types, etiology and mechanisms of formation.

The study of the composition and structure of 41 stones composed of uric acid was complemented by in vitro investigation of the crystallization of uric acid. Uric acid dihydrate (UAD) precipitates from synthetic urine under physiological conditions when the medium is supersaturated with respect to this compound, though uric acid anhydrous (UAA) represents the thermodynamically stable form. Solid UAD in contact with liquid transforms into UAA within 2 days. This transition is accompanied by development of hexagonal bulky crystals of UAA and appearance of cracks in the UAD crystals. Uric acid calculi can be classified into two groups, differing in outer appearance and inner structure. Type I includes stones with a little central core and a compact columnar UAA shell and stones with interior structured in alternating densely non-columnar layers developed around a central core; both of them are formed mainly by crystalline growth at low uric acid supersaturation. Type II includes porous stones without inner structure and stones formed by a well developed outermost layer with an inner central cavity; this type of stones is formed mainly by sedimentation of uric acid crystals generated at higher uric acid supersaturation.

Ammonium and sodium urates precipitating from synthetic urine and fine structure of urate renal calculi.

A study of ammonium and sodium urate precipitation in vitro and the fine structure of several urate renal calculi was carried out to contribute to an understanding of the participation of ammonium and sodium urates in urolithiasis. Ammonium urate precipitated in vitro in two different morphologies: a typical spherulite morphology formed at high supersaturation and disorganized needle-like crystals formed at low supersaturation. In all cases sodium urate precipitated in vitro as bundles of curved fibrils, its crystallization being inhibited by calcium in concentrations between 20 and 60 mg/l depending on the sodium urate supersaturation. From a collection of 1300 renal calculi, only three had ammonium urate as their main component (0.2%), three were mixed calculi (0.2%) consisting of ammonium urate and calcium oxalate (two) or uric acid (one), and in one calculus ammonium urate was present as a minor component. Only in a mixed calculus of uric acid and calcium oxalate was sodium urate detected in a very low quantity. The study of the fine structure of the renal calculi constituted mainly by ammonium urate demonstrated similar patterns in which spherulites, needle-like individual crystals and an amorphous mass of ammonium urate with abundant organic matter in non-organized structures coexist. As minor components, struvite or calcium oxalate crystals were found. A general mechanism of the formation of such calculi is proposed.

Structure of uric acid concretion developed around a catheter.

A uric acid concretion formed round a catheter (JJ stent) in the bladder and removed intact from the body together with the catheter was studied using an electron scanning microscope. The concretion was composed of anhydrous uric acid, some uric acid dihydrate (< 5 wt.%) and individual particles of calcium oxalate monohydrate. The stone interior was porous with frequent occurrence of differently sized cavities that were either empty or partially filled with particles of uric acid and/or calcium oxalate monohydrate. Calcium oxalate particles were not of crystalluria origin but developed in the cavity. The succession of processes leading to the stone formation was deduced from its inner structure. The stone was formed due to a crystalline growth with minor, if any, participation of sedimentation. The estimated average rate of the calculus development, 2 x 10(-9) m/s, confirms the predominant role of crystalline growth in stone formation and indicates a relatively low urinary supersaturation with respect to uric acid prevailing during the period of calculogenesis.

Uric acid urolithiasis and crystallization inhibitors.

An in vitro study of the inhibitory effects that some substances occasionally present in urine can provoke on the crystallization of uric acid has been performed. The most remarkable crystallization inhibitory effects were produced by mucine at concentrations of >0.5 mg/l. Pentosan polysulfate and chondroitin sulfate also clearly increased the uric acid crystallization times at concentrations of >100 mg/l. Saponins, such as escin and glycyrrhizic acid, also produced a notable delay in uric acid crystallization times at concentrations of >10 mg/l. Similar effects were observed in the presence of a surfactant substance, lauryl sulfate. N-Acetyl-L-cysteine caused crystallization perturbations only when it was present at concentrations of >50 mg/l. Citric acid and phytic acid caused no effects on uric acid crystallization even at the highest concentrations assayed (1,000 and 5 mg/l, respectively). From the results obtained it can be deduced that mainly glycoproteins, glycosaminoglycans and surfactant substances can exert protective effects against uric acid crystallization.

Mortalidad perinatal. Distribución según la edad gestacional y el peso al nacimiento. Causas más frecuentes. Revisión epidemiológica de 10 años / Perinatal mortality. Birth weight and gestational age distribution. Most frequent causes of death. A ten year epidemiological review

Objetivos: Evaluar la mortalidad perinatal (MP) de los últimos 10 años (1994-2003) habida en el Servicio de Obstetricia del Hospital Miguel Servet de Zaragoza. Se distribuye según la edad gestacional y el peso al nacimiento. Se analizan las posibles causas tanto maternas como fetales que pudieran estar implicadas. Material y métodos: Sobre un total de 37.665 recién nacidos (RN) de más de 500 g de peso, hubo 368 nacidos muertos o que fallecieron antes de los 28 días completos de vida. El Hospital Materno-infantil es un centro de referencia (nivel terciario) para las comunidades de Aragón y La Rioja, para la provincia de Soria y para los RN o sus madres con problemas procedentes de la actividad privada local. Resultados: La MP global es del 9,770/00. Para las comparaciones internacionales, la MP I (> 28 semanas y hasta 7 días de vida) es del 5,620/00. Según la edad gestacional, un 72,28 por ciento son RN pretérmino, la mitad (50 por ciento) con menos de 32 semanas de gestación. Por pesos al nacimiento, la MP está gravada por la gran inmadurez: un 36,68 por ciento de los RN con un peso < 1.000 g y un 51,90 por ciento < 1.500 g, 70 RN proceden de partos múltiples y todos ellos son pretérmino. La MP de los partos múltiples es globalmente del 46,510/00 (el 42,790/00 en gemelos). Las causas fetales más frecuentes son la asfixia y la anoxia antes del inicio del trabajo de parto (26,84 por ciento), la inmadurez extrema, tener un peso < 1.000 g (16,30 por ciento) y la patología respiratoria (12,22 por ciento). Las causas maternas más frecuentes son las gestaciones múltiples (19,02 por ciento), la rotura prematura de las membranas (12,22 por ciento) y el desprendimiento prematuro de la placenta y la hemorragia placentaria (10,05 por ciento) (AU)