Potential Application of A Synthetic Organo-funtionalized High Load Expandable Mica as A Drug Carrier for Controlled Release.

BACKGROUND: In this work the cytotoxicity and gastric and gastrointestinal resistance of a high-load synthetic expandable mica, Na-mica-4, is studied for the first time. The hydrophilic character of this clay mineral can be modified by ion exchange reaction between Na+ inorganic cations housed in the interlayer space, and surfactant molecules, resulting in the formation of an organophilic material. This adsorption capability of organic compounds makes them very useful for a wide range of applications, such as their use as drug carriers. Previous studies have shown the high adsorption capacity of organofunctionalized Na-mica-4 of different types of drugs. Objetive: To carry out initial trials aimed at testing the cytotoxicity of a synthetic organofunctional expandable mica and evaluating its resistance to gastric and gastrointestinal digestion. METHODS: A highly charged sodium mica (Na-mica-4) was synthesized and organofunctional by cationic exchange with an alkylamine, primary amine of 18 carbon atoms (C18-mica-4). Both were characterized by X-ray diffraction, field transmission electron microscopy, surface-specific analysis, differential scanning calorimetry, and thermal gravimetric analysis. In addition, screening cytotoxicity trials were conducted on the human intestinal cell line Caco-2 with C18-mica-4 (0-125 µg/ml). RESULTS: Only one of the endpoints evaluated (the reduction of tetrazolium MTS salt by dehydrogenase enzymes) showed a significant decrease in cellular viability after 48h at the highest concentration tested. C18-mica-4 shows structural resistance to both, gastric and gastrointestinal, digestion. CONCLUSION: A successful development of a functionalized mica has been made with a promising potential application as a carrier to the drug.

Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice.

BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is a hedgehog-target, and a cytokine that is highly upregulated in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesised that OPN may modulate liver progenitor cell response, and thereby, modulate fibrotic outcomes. We further evaluated the impact of OPN-neutralisation on murine liver fibrosis. METHODS: Liver progenitors (603B and bipotential mouse oval liver) were treated with OPN-neutralising aptamers in the presence or absence of transforming growth factor (TGF)-ß, to determine if (and how) OPN modulates liver progenitor function. Effects of OPN-neutralisation (using OPN-aptamers or OPN-neutralising antibodies) on liver progenitor cell response and fibrogenesis were assessed in three models of liver fibrosis (carbon tetrachloride, methionine-choline deficient diet, 3,5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by quantitative real time (qRT) PCR, Sirius-Red staining, hydroxyproline assay, and semiquantitative double-immunohistochemistry. Finally, OPN expression and liver progenitor response were corroborated in liver tissues obtained from patients with chronic liver disease. RESULTS: OPN is overexpressed by liver progenitors in humans and mice. In cultured progenitors, OPN enhances viability and wound healing by modulating TGF-ß signalling. In vivo, OPN-neutralisation attenuates the liver progenitor cell response, reverses epithelial-mesenchymal-transition in Sox9+ cells, and abrogates liver fibrogenesis. CONCLUSIONS: OPN upregulation during liver injury is a conserved repair response, and influences liver progenitor cell function. OPN-neutralisation abrogates the liver progenitor cell response and fibrogenesis in mouse models of liver fibrosis.

Multiparametric immunotoxicity screening in mice during early drug development.

Evaluation of potential adverse effects on the immune system should be incorporated into drug development prior to phase III clinical trials. In addition to standard toxicity results, T-dependent antibody response (TDAR) assays are widely used to evidence impaired immune function. The present study was aimed at validating a multiparametric screening approach in mice to investigate exaggerated pharmacologic or unintended immunosuppressive effects in early drug development. Male CD1 mice injected with a single IV dose of 2mg KLH displayed a robust anti-KLH IgM response that peaked on day +5. Anti-KLH IgM response, standard haematology parameters, and thymus/spleen weight and histology were examined in mice treated once daily for 4 days with cyclophosphamide (CY; 5-20mg/kg/day), cyclosporine (CS; 10-90mg/kg/day), dexamethasone (DX; 5-20mg/kg/day), prednisolone (PR; 3-30mg/kg/day) or chlorpromazine (CZ; 10-30mg/kg/day). CY and CS decreased anti-KLH IgM response at all dose levels. CY induced a marked decrease in WBC count and thymus/spleen weight with histological changes in both lymphoid organs. CS mainly decreased thymus weight (highest dose), which was associated with lymphoid depletion, without relevant effects on haematology parameters. Neither DX nor PR nor CZ induced significant changes in anti-KLH IgM response. DX and PR decreased lymphocyte counts and thymus/spleen weight, and induced histological changes in both lymphoid organs. CZ (higher doses) decreased lymphocyte count and thymus weight, and induced consistent histological changes in the thymus. This multiparametric study was able to detect 5 human drugs with variable immunosuppressive potency and thus may prove to be a useful early screening tool for predicting drug immunotoxicity.

Synthetic high-charge organomica: effect of the layer charge and alkyl chain length on the structure of the adsorbed surfactants.

A family of organomicas was synthesized using synthetic swelling micas with high layer charge (Na(n)Si(8-n)Al(n)Mg(6)F(4)O(20)·XH(2)O, where n = 2, 3, and 4) exchanged with dodecylammonium and octadecylammonium cations. The molecular arrangement of the surfactant was elucidated on the basis on XRD patterns and DTA. The ordering conformation of the surfactant molecules into the interlayer space of micas was investigated by (13)C, (27)Al, and (29)Si MAS NMR. The arrangement of alkylammonium ions in these high-charge synthetic micas depends on the combined effects of the layer charge of the mica and the chain length of the cation. In the organomicas with dodecylammonium, a transition from a parallel layer to a bilayer-paraffin arrangement is observed when the layer charge of the mica increases. However, when octadecylammonium is the interlayer cation, the molecular arrangement of the surfactant was found to follow the bilayer-paraffin model for all values of layer charge. The amount of ordered conformation all-trans is directly proportional of layer charge.

Remediation of metal-contaminated soils with the addition of materials - part II: leaching tests to evaluate the efficiency of materials in the remediation of contaminated soils.

The effect of the addition of materials on the leaching pattern of As and metals (Cu, Zn, Ni, Pb, and Cd) in two contaminated soils was investigated. The examined materials included bentonites, silicates and industrial wastes, such as sugar foam, fly ashes and a material originated from the zeolitization of fly ash. Soil + material mixtures were prepared at 10% doses. Changes in the acid neutralization capacity, crystalline phases and contaminant leaching over a wide range of pHs were examined by using pH(stat) leaching tests. Sugar foam, the zeolitic material and MX-80 bentonite produced the greatest decrease in the leaching of pollutants due to an increase in the pH and/or the sorption capacity in the resulting mixture. This finding suggests that soil remediation may be a feasible option for the reuse of non-hazardous wastes.

Remediation of metal-contaminated soils with the addition of materials--part I: characterization and viability studies for the selection of non-hazardous waste materials and silicates.

Contamination episodes in soils require interventions to attenuate their impact. These actions are often based on the addition of materials to increase contaminant retention in the soil and to dilute the contaminant concentration. Here, non-hazardous wastes (such as sugar foam, fly ash and a material produced by the zeolitization of fly ash) and silicates (including bentonites) were tested and fully characterized in the laboratory to select suitable materials for remediating metal-contaminated soils. Data from X-ray fluorescence (XRF), N(2) adsorption/desorption isotherms, X-ray diffraction (XRD) and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM-EDX) analyses revealed the chemical composition, specific surface area and the phases appearing in the materials. A pH titration test allowed the calculation of their acid neutralization capacity (ANC). The metal sorption and desorption capacities of the waste materials and silicates were also estimated. Sugar foam, fly ash and the zeolitic material were the best candidate materials. Sugar foam was selected because of its high ANC (17000 meq kg(-1)), and the others were selected because of their larger distribution coefficients and lower sorption reversibilities than those predicted in the contaminated soils.

Formation of organo-highly charged mica.

The interlayer space of the highly charged synthetic Na-Mica-4 can be modified by ion-exchange reactions involving the exchange of inorganic Na(+) cations by surfactant molecules, which results in the formation of an organophilic interlayer space. The swelling and structural properties of this highly charged mica upon intercalation with n-alkylammonium (RNH(3))(+) cations with varying alkyl chain lengths (R = C12, C14, C16, and C18) have been reported. The stability, fine structure, and evolution of gaseous species from alkylammonium Mica-4 are investigated in detail by conventional thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), in situ X-ray diffraction (XRD), and solid-state nuclear magnetic resonance (MAS NMR) techniques. The results clearly show the total adsorption of n-alkylammonium cations in the interlayer space which expands as needed to accommodate intercalated surfactants. The surfactant packing is quite ordered at room temperature, mainly involving a paraffin-type bilayer with an all-trans conformation, in agreement with the high density of the organic compounds in the interlayer space. At temperatures above 160 °C, the surfactant molecules undergo a transformation that leads to a liquid-like conformation, which results in a more disordered phase and expansion of the interlayer space.

An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats

There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP) and the heart rate (HR) of all rats were measured systematically before (over 1 h) and after three consecutive iv bolus injections of phenylephrine (PHE) and sodium nitroprusside (SNP). Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope) were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a) neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b) even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI)] and SNP-PHE slope [transformed general sensitivity index (TGSI), {((3-(ΔHRSNP-ΔHRPHE/ΔMAPSNP-ΔMAPPHE))-0.4-1)/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c) TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46), aortic (8.40 to 9.94) and sino-aortic (7.68 to 8.24) barodenervated conscious rats were defined.

An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats.

There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP) and the heart rate (HR) of all rats were measured systematically before (over 1 h) and after three consecutive iv bolus injections of phenylephrine (PHE) and sodium nitroprusside (SNP). Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope) were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a) neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b) even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI)] and SNP-PHE slope [transformed general sensitivity index (TGSI), {((3-(ΔHR(SNP)-ΔHR(PHE)/ΔMAP(SNP)-ΔMAP(PHE)))(-0.4)-1)/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c) TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46), aortic (8.40 to 9.94) and sino-aortic (7.68 to 8.24) barodenervated conscious rats were defined.

Neuropharmacological study of hetero[2,1]benzothiazepine derivatives analogues of tianeptine.

Neuropharmacological studies were conducted in mice with a number of hetero[2,1]benzothiazepine derivatives, analogues of tianeptine. Seven of the 12 compounds under study potentiated the actions of 5-hydroxytryptophan (5-HTP, 50 mg/kg i.p.) and/or antagonised the hypothermia induced by high doses of apomorphine. Moreover, some of them inhibited the head twitches induced by 5-HTP (250 mg/kg i.p.) and the stereotyped behaviour and/or climbing behaviour of low doses of apomorphine. These compounds also produced a slight inhibition of exploratory behaviour in the holeboard test. On the other hand, no significant muscle relaxant, anticonvulsant and anxiolytic activities were observed at any dose employed. Together, these data suggest that some of the compounds under study exert antidepressant and neuroleptic effects in mice with no muscle relaxant, anxiolytic and anticonvulsant activities.

Alveolitis alérgica extrínseca por exposición a un humidificador ultrasónico / Extrinsic allergic alveolitis due to exposure to an ultrasound humidifier

La alveolitis alérgica extrínseca es una entidad con frecuencia de origen ocupacional, que afecta al parénquima pulmonar y progresa hacia fibrosis en estadios avanzados si no se diagnostica de forma precoz. Requiere para su diagnóstico una anamnesis detallada en la búsqueda del agente etiológico. Se ha estudiado a un paciente con cuadros repetidos de infiltrados pulmonares que simulaban neumonías y se trataban con antibióticos. El diagnóstico, tras realizar un detallado estudio, fue el de alveolitis alérgica extrínseca desencadenada por un antígeno de origen no ocupacional debido a los contaminantes probablemente fúngicos de un humidificador ultrasónico en el domicilio del paciente, utilizado para el tratamiento de cuadros de bronquiolitis de repetición de su hijo. Se objetivó infiltración bibasal en la tomografía computadorizada, restricción acusada en la espirometría y anticuerpos precipitantes contra los restos del humidificador; el paciente realizó una provocación involuntaria con exposición al humidificador en su domicilio tras ser dado de alta del último episodio. En el cultivo realizado con los residuos del humidificador crecieron varios hongos: Candida albicans, Aspergillus fumigatus y Rhodotorula rubra. Se obtuvo anticuerpos precipitantes frente a C. albicans. En el ELISA inhibición la IgG específica frente a componentes del humidificador se inhibió el 10 por ciento por C. albicans y no se obtuvo inhibición por R. rubra. Dada la ubicuidad de C. albicans y su escasa participación en los anticuerpos contra los contaminantes del humidificador, no puede confirmarse como agente etiológico. El paciente quedó totalmente asintomático al retirar el aparato de su domicilio. (AU)

Synthesis and preliminary pharmacological evaluation of thiophene analogues of viloxazine as potential antidepressant drugs.

A series of eight thienyloxymethylmorpholines, thiophene analogues of viloxazine, have been synthesized by three different routes. The preliminary pharmacological evaluation of this series shows antidepressant properties on the mice models used with a light sedative action. The structure-activity relationship is established in a first approximation.

[Barrett esophagus. An epidemiological study in an area of Spain]. / Esófago de Barrett. Estudio epidemiológico en una comarca.

Barrett's esophagus is defined as the replacement of squamous normal mucosa by columnar specialized epithelium, being its main importance its preneoplastic potential. In this retrospective study on 5303 gastrointestinal endoscopies, done in 8 years, we describe, for the first time the gross prevalence and incidence rates in a Spanish country. We found 28 cases of Barrett's esophagus, what means a prevalence rate of 0.53% of all endoscopies, and an incidence rate of 26.4/100,000 inhabitants of our hospital referred population, with an estimated incidence rate of 3.3 cases/100,000 inhabitants/year. The prevalence rate of Barrett's esophagus adenocarcinoma--3 cases--was 10.71%, and the incidence rate of 1 case/104 Barrett's esophagus/year, follow-up similar to that of other authors.

[Resolution with steroid therapy of an idiopathic esophageal fistula in a patient with AIDS]. / Resolución con tratamiento esteroideo de una fístula esofágica idiopática en un paciente con SIDA.

We present a case of AIDS with idiopathic esophagic fistula which had a positive response to steroid therapy. We discuss the diagnostic potential and the therapeutic attitude in these cases.

Efecto de la formulación de los detergentes en la calidad del agua en México por el tipo de surfactante y por el contenido de fosforo

Este trabajo tiene como objetivo determinar que los detergentes han impactado al recurso hidráulico de 3 de las cuencas mas contaminadas de México dentro del sistema integral que considera no solo su presencia en el agua residual y en las plantas de tratamiento sino tambien en las plantas potabilizadoras que se abastecen de estos cuerpos de agua superficial; y que en determinadas epocas aun operando con altas eficiencias el sistema de tratamiento especifico, para solucionar el problema a corto plazo

[Granular cell tumor of the esophagus]. / Tumor de células granulosas de esófago.

Granular cell tumor is a neoplasm usually benign, which only in two percent of the cases affects the esophagus. Histologically it is composed by two kind of cells: granular and angled body cells. The histogenesis of this tumor remains controversial; however, it has been recently demonstrated, by immunohistochemical methods, the presence of proteins that are specific of the nervous system. The diagnosis is frequently done incidentally and by endoscopic biopsy. We report a case of granular cell tumor of the distal esophagus found incidentally during a routine endoscopic examination. We review the English and Spanish literatures, focussing on the histological and diagnostic peculiarities. The clinical management and the different available therapeutics, according to symptoms and tumor size, are discussed.

Synthesis and preliminary pharmacological study of thiophene analogues of the antipyretic and analgesic agent ethenzamide.

A preliminary pharmacological study of a thiophene analogue 1b of the analgesic and antipyretic agent Ethenzamide and of a closely related compound 1a showed that a great similarity exists among Ethenzamide and the thiophenic compounds for analgesic, antipyretic, ulcerogenic, hypothermic, and sedative effects. However, the acute toxicity in mice for the thiophenic compounds is notably higher than that of Ethenzamide.